Patient Perspectives on a Patient-Facing Tool for Lung Cancer Screening.

BACKGROUND: Individuals with high risk for lung cancer may benefit from lung cancer screening, but there are associated risks as well as benefits. Shared decision-making (SDM) tools with personalized information may provide key support for patients. Understanding patient perspectives on educational tools to facilitate SDM for lung cancer screening may support tool development. AIM: This study aimed to explore patient perspectives related to a SDM tool for lung cancer screening using a qualitative approach. METHODS: We elicited patient perspectives by showing a provider-facing SDM tool. Focus group interviews that ranged in duration from 1.5 to 2 h were conducted with 23 individuals with high risk for lung cancer. Data were interpreted inductively using thematic analysis to identify patients' thoughts on and desires for a patient-facing SDM tool. RESULTS: The findings highlight that patients would like to have educational information related to lung cancer screening. We identified several key themes to be considered in the future development of patient-facing tools: barriers to acceptance, preference against screening and seeking empowerment. One further theme illustrated effects of patient-provider relationship as a limitation to meeting lung cancer screening information needs. Participants also noted several suggestions for the design of technology decision aids. CONCLUSION: These findings suggest that patients desire additional information on lung cancer screening in advance of clinical visits. However, there are several issues that must be considered in the design and development of technology to meet the information needs of patients for lung cancer screening decisions. PATIENT OR PUBLIC CONTRIBUTION: Patients, service users, caregivers or members of the public were not involved in the study design, conduct, analysis or interpretation of the data. However, clinical experts in health communication provided detailed feedback on the study protocol, including the focus group approach. The study findings contribute to a better understanding of patient expectations for lung cancer screening decisions and may inform future development of tools for SDM.

ACVR1/ALK2-p21 signaling axis modulates proliferation of the venous endothelium in the retinal vasculature.

The proliferation of the endothelium is a highly coordinated process to ensure the emergence, expansion, and homeostasis of the vasculature. While Bone Morphogenetic Protein (BMP) signaling fine-tunes the behaviors of endothelium in health and disease, how BMP signaling influences the proliferation of endothelium and therefore, modulates angiogenesis remains largely unknown. Here, we evaluated the role of Activin A Type I Receptor (ACVR1/ALK2), a key BMP receptor in the endothelium, in modulating the proliferation of endothelial cells. We show that ACVR1/ALK2 is a key modulator for the proliferation of endothelium in the retinal vessels. Loss of endothelial ALK2 leads to a significant reduction in endothelial proliferation and results in fewer branches/endothelial cells in the retinal vessels. Interestingly, venous endothelium appears to be more susceptible to ALK2 deletion. Mechanistically, ACVR1/ALK2 inhibits the expression of CDKN1A/p21, a critical negative regulator of cell cycle progression, in a SMAD1/5-dependent manner, thereby enabling the venous endothelium to undergo active proliferation by suppressing CDKN1A/p21. Taken together, our findings show that BMP signaling mediated by ACVR1/ALK2 provides a critical yet previously underappreciated input to modulate the proliferation of venous endothelium, thereby fine-tuning the context of angiogenesis in health and disease.

Large-Scale Proteomics in Early Pregnancy and Hypertensive Disorders of Pregnancy.

Importance: There is no consensus regarding the best method for prediction of hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia. Objective: To determine predictive ability in early pregnancy of large-scale proteomics for prediction of HDP. Design, Setting, and Participants: This was a nested case-control study, conducted in 2022 to 2023, using clinical data and plasma samples collected between 2010 and 2013 during the first trimester, with follow-up until pregnancy outcome. This multicenter observational study took place at 8 academic medical centers in the US. Nulliparous individuals during first-trimester clinical visits were included. Participants with HDP were selected as cases; controls were selected from those who delivered at or after 37 weeks without any HDP, preterm birth, or small-for-gestational-age infant. Age, self-reported race and ethnicity, body mass index, diabetes, health insurance, and fetal sex were available covariates. Exposures: Proteomics using an aptamer-based assay that included 6481 unique human proteins was performed on stored plasma. Covariates were used in predictive models. Main Outcomes and Measures: Prediction models were developed using the elastic net, and analyses were performed on a randomly partitioned training dataset comprising 80% of study participants, with the remaining 20% used as an independent testing dataset. Primary measure of predictive performance was area under the receiver operating characteristic curve (AUC). Results: This study included 753 HDP cases and 1097 controls with a mean (SD) age of 26.9 (5.5) years. Maternal race and ethnicity were 51 Asian (2.8%), 275 non-Hispanic Black (14.9%), 275 Hispanic (14.9%), 1161 non-Hispanic White (62.8% ), and 88 recorded as other (4.8%), which included those who did not identify according to these designations. The elastic net model, allowing for forced inclusion of prespecified covariates, was used to adjust protein-based models for clinical and demographic variables. Under this approach, no proteins were selected to augment the clinical and demographic covariates. The predictive performance of the resulting model was modest, with a training set AUC of 0.64 (95% CI, 0.61-0.67) and a test set AUC of 0.62 (95% CI, 0.56-0.68). Further adjustment for study site yielded only minimal changes in AUCs. Conclusions and Relevance: In this case-control study with detailed clinical data and stored plasma samples available in the first trimester, an aptamer-based proteomics panel did not meaningfully add to predictive utility over and above clinical and demographic factors that are routinely available.

Interplay of Race and Neighborhood Deprivation on Resting and Ambulatory Blood Pressure in Young Adults.

BACKGROUND: Nighttime BP and BP dipping (daytime-nighttime BP) are prognostic for cardiovascular disease. Compared with other racial/ethnic groups, Black Americans exhibit elevated nighttime BP and attenuated BP dipping. Neighborhood deprivation may contribute to disparities in cardiovascular health, but its effects on resting and ambulatory BP patterns in young adults is unclear. Therefore, we examined associations between neighborhood deprivation with resting and nighttime BP and BP dipping in young Black and White adults. METHODS: We recruited 19 Black and 28 White participants (23 M/24 F, 21±1 years, body mass index: 26±4 kg/m2) for 24-hour ambulatory BP monitoring. We assessed resting BP, nighttime BP, and BP dipping (absolute dip and nighttime:daytime BP ratio). We used the area deprivation index (ADI) to assess average neighborhood deprivation during early- and mid-childhood, and adolescence. RESULTS: Compared with White participants, Black participants exhibited higher resting systolic and diastolic BP (ps≤0.029), nighttime systolic BP (114±9 vs. 108±9 mmHg, p=0.049), diastolic BP (63±8 vs. 57±7 mmHg, p=0.010), and attenuated absolute systolic BP dipping (12±5 vs. 9±7 mmHg, p=0.050). Black participants experienced greater average ADI scores compared with White participants (110(10) vs. 97(22), p=0.002), and select ADI scores correlated with resting BP and some ambulatory BP measures. Within each race, select ADI scores correlated with some BP measures for Black participants, but there were no ADI and BP correlations for White participants. CONCLUSIONS: Our findings suggest neighborhood deprivation may contribute to higher resting BP and impaired ambulatory BP patterns in young adults warranting further investigation in larger cohorts.

Geographic Trends in Ophthalmology Resident Physician Compensation and Cost-of-Living Expenses.

Importance: Given that resident physician financial strain has been associated with poor outcomes, objective metrics to forecast financial well-being may be useful to (1) applicants when evaluating ophthalmology residency programs and (2) programs when determining resident benefits. Objectives: To determine and compare the relative value of ophthalmology resident stipends plus benefits when adjusted for cost-of-living expenses and to analyze program characteristics associated with greater resident net incomes. Design, Setting, and Participants: In this cross-sectional study, the American Medical Association's Fellowship and Residency Electronic Interactive Database was used to identify US Accreditation Council for Graduate Medical Education-accredited ophthalmology residency programs. Resident physician stipends and stipends plus benefits as well as residency program characteristics from the 2023-2024 academic year were noted for all eligible programs. The Massachusetts Institute of Technology's Living Wage Calculator's required annual income (RAI) was selected as a surrogate to approximate cost-of-living expenses. Exposure: Residency program characteristics, including affiliation, size, ranking, presence of housing benefit, and training year. Main Outcomes and Measures: The primary outcome was the annual stipend plus benefits income surplus (SPBIS) for each residency program, defined as the resident's stipend plus benefits (SPB) minus the RAI for the county in which the residency program is located. Secondary outcomes included income surplus variation by program characteristics. Results: Of 116 ophthalmology residency programs analyzed, 37 (31.9%) were located in the Northeast, 36 (31.0%) in the South, 29 (25.0%) in the Midwest, and 14 (12.1%) in the West. The mean (SD) postgraduate year 1 resident annual SPB was $65 397 ($8205), and the median (IQR) was $63 986 ($59 992-$69 698). After adjusting for the cost of living, the mean (SD) SPBIS was $27 459 ($5734) and the median (IQR) was $27 380 ($23 625-$31 796). Annual cost-of-living expenses varied by as much as $8628 (95% CI, $6310-$10 947) and SPBIS varied by as much as $6283 (95% CI, $3367-$9198) between regions. Resident SPB increased by a mean (SD) of 3.97% (0.98%) for each subsequent training year (range, 0.93%-7.26%). Annual SPBIS increased by a mean (SD) of 9.48% (3.60%) for each subsequent training year. Conclusions and Relevance: After adjusting for living costs, intraregional and interregional differences in SPBIS among ophthalmology residents can vary by thousands of dollars, impacting residents' financial security. Further discussion regarding compensation may lead to innovative strategies that aim to improve resident well-being and performance.

Bidirectional activation of stem-like programs between metastatic cancer and alveolar type 2 cells within the niche.

A key step for metastatic outgrowth involves the generation of a deeply altered microenvironment (niche) that supports the malignant behavior of cancer cells. The complexity of the metastatic niche has posed a significant challenge in elucidating the underlying programs driving its origin. Here, by focusing on early stages of breast cancer metastasis to the lung in mice, we describe a cancer-dependent chromatin remodeling and activation of developmental programs in alveolar type 2 (AT2) cells within the niche. We show that metastatic cells can prime AT2 cells into a reprogrammed multilineage state. In turn, this cancer-induced reprogramming of AT2 cells promoted stem-like features in cancer cells and enhanced their initiation capacity. In conclusion, we propose the concept of "reflected stemness" as an early phenomenon during metastatic niche initiation, wherein metastatic cells reprogram the local tissue into a stem-like state that enhances intrinsic cancer-initiating potential, creating a positive feedback loop where tumorigenic programs are amplified.

SHC-3: a previously unidentified C. elegans Shc family member functions in the insulin-like signaling pathway to enhance survival during L1 arrest.

Shc proteins function in many different signaling pathways where they mediate phosphorylation-dependent protein-protein interactions. These proteins are characterized by the presence of two phosphotyrosine-binding domains, an N-terminal PTB and a C-terminal SH2. We describe a previously unrecognized C. elegans Shc gene, shc-3 and characterize its role in stress response. Both shc-3 and shc-1 are required for long-term survival in L1 arrest and survival in heat stress, however, they do not act redundantly but rather play distinct roles in these processes. Loss of shc-3 did not further decrease survival of daf-16 mutants in L1 arrest, suggesting that like SHC-1, SHC-3 functions in the Insulin-like signaling pathway. In the absence of SHC-3, DAF-16 nuclear entry and exit are slowed, suggesting that SHC-3 is required for rapid changes in DAF-16 signaling.

The interictal suppression hypothesis is the dominant differentiator of seizure onset zones in focal epilepsy.

Successful surgical treatment of drug-resistant epilepsy traditionally relies on the identification of seizure onset zones (SOZs). Connectome-based analyses of electrographic data from stereo electroencephalography (SEEG) may empower improved detection of SOZs. Specifically, connectome-based analyses based on the Interictal Suppression Hypothesis (ISH) posit that when the patient is not having a seizure, SOZs are inhibited by non-SOZs through high inward connectivity and low outward connectivity. However, it is not clear whether there are other motifs that can better identify potential SOZs. Thus, we sought to use unsupervised machine learning to identify network motifs that elucidate SOZs and investigate if there is another motif that outperforms the ISH. Resting-state SEEG data from 81 patients with drug-resistant epilepsy undergoing a pre-surgical evaluation at Vanderbilt University Medical Center were collected. Directed connectivity matrices were computed using the alpha band (8-12Hz). Principal component analysis (PCA) was performed on each patient's connectivity matrix. Each patient's components were analyzed qualitatively to identify common patterns across patients. A quantitative definition was then used to identify the component that most closely matched the observed pattern in each patient. A motif characteristic of the Interictal Suppression Hypothesis (high-inward and low-outward connectivity) was present in all individuals and found to be the most robust motif for identification of SOZs in 64/81 (79%) patients. This principal component demonstrated significant differences in SOZs compared to non-SOZs. While other motifs for identifying SOZs were present in other patients, they differed for each patient, suggesting that seizure networks are patient specific, but the ISH is present in nearly all networks. We discovered that a potentially suppressive motif based on the Interictal Suppression Hypothesis was present in all patients, and it was the most robust motif for SOZs in 79% of patients. Each patient had additional motifs that further characterized SOZs, but these motifs were not common across all patients. This work has the potential to augment clinical identification of SOZs to improve epilepsy treatment.

Outcomes Associated With Giant Coronary Artery Aneurysms After Kawasaki Disease: A Single-Center United States Experience.

OBJECTIVE: To determine the long-term outcomes among a cohort of patients with Kawasaki disease (KD) and a history of giant coronary artery aneurysms (CAA) at a single US center. RESULTS: There were 60 patients with KD and giant CAAs identified between 1989 and 2023. The majority of patients were male (71.7%) with median age at diagnosis of 0.9 years (0.2-13.3). Patients were followed for a median of 11 years, up to 34.5 years. MACE occurred in 13 (21.7%) patients at a median of 1.4 years (0.04-22.6) after KD diagnosis. The 10-, 20-, and 30-year MACE-free rates were 75%, 75%, and 60%. Patients with maximal CA z-scores ≥20 or bilateral CAA were more likely to have MACE. During follow-up, 26.7% of CAA regressed to normal luminal diameter at a median of 3.6 years (0.6-12.0). The 10-, 20- and 30-year likelihood of CA regression to normal luminal diameter was 36%, 46%, and 46%. CONCLUSIONS: Over 30 years, MACE occurred in nearly 22% of patients, more often in those with bilateral CAA or CA z-scores ≥20. Despite regression to normal luminal diameter in over 25% of CAA, patients with a history of KD-associated giant CAA require ongoing surveillance for cardiac complications, even years after the initial disease.

Effects of Weight Loss on Key Obesity-Related Biomarkers Linked to the Risk of Endometrial Cancer: A Systematic Review and Meta-Analysis.

Endometrial cancer (EC) includes various histologic types, with estrogen-dependent endometrioid carcinoma being the most common. Obesity significantly increases the risk of developing this type, especially in postmenopausal women, due to elevated estrogen production by adipocytes. This review examines the impact of weight loss from different interventions on reducing obesity-related risk factors for endometrioid EC. A systematic review and meta-analysis were conducted on three weight loss interventions: bariatric surgery, pharmacotherapy, and lifestyle changes. The effects of these interventions on inflammatory biomarkers (CRP, TNF-α, IL-6) and hormones (leptin, estrogen) were analyzed. Data from controlled studies were pooled to assess the significance of weight loss in reducing these biomarkers. Despite heterogeneity, bariatric surgery resulted in an overall 25.8% weight reduction, outperforming lifestyle and pharmacotherapy interventions. Weight loss reduced CRP levels by 33.5% and IL-6 levels by 41.9%. TNF-α levels decreased by 13% with percent weight loss over 7%. Leptin levels also decreased significantly, although the exact weight loss percentage was not statistically significant. Weight loss effectively reduces proinflammatory markers and hormones associated with increased risk of endometrioid EC. The strengths of this review include a comprehensive examination of different weight-loss interventions and a large pool of participants. However, limitations include high heterogeneity among studies and only 43% of the participants being postmenopausal. Limited data on sex hormones and racial disparities underscore the need for further research.

Genomic and Phenotypic Safety Assessment of Probiotic Bacillus coagulans Strain JBI-YZ6.3.

Spore-forming Bacillus coagulans has been widely recognized as an important probiotic, which is commonly used in products for human consumption and animal feeds. B. coagulans exhibits beneficial traits from both Bacillus and lactic acid-producing Lactobacillus. The present study evaluated the safety of the newly isolated B. coagulans strain JBI-YZ6.3, using combined genomic and phenotypic analysis approaches. The taxonomic classification based on genome sequence and biochemical tests identified strain JBI-YZ6.3 as B. coagulans. Comprehensive genome-based analyses established JBI-YZ6.3 as a novel strain of B. coagulans. Antibiotic susceptibility testing showed that the strain JBI-YZ6.3 was sensitive to a panel of fourteen antibiotics, and no genes related to antibiotic resistance were found in its genome. The spores of strain JBI-YZ6.3 exhibited tolerance to acid and bile salts, as well as stability at ambient and elevated conditions of temperature and relative humidity. There were no homologs of Bacillus toxin genes identified in the genome of JBI-YZ6.3, and the strain exhibited no cytotoxicity towards Vero cells and human peripheral blood mononuclear cells. In conclusion, findings from this study support the safety of B. coagulans strain JBI-YZ6.3, which can be developed into new probiotic products for preventive and therapeutic benefits in human and animal hosts.

Health Care Utilization Prior to Ovarian Cancer Diagnosis in Publicly Insured Individuals in New York State.

Background: Women with early-stage ovarian cancer may be asymptomatic or present with nonspecific symptoms. We examined health care utilization prior to ovarian cancer diagnosis to assess whether women with higher utilization differed in their prognosis and outcomes compared to women with low utilization. Methods: Using Medicaid, Medicare, and New York State Cancer Registry data for ovarian cancer cases diagnosed in 2006-2015, we examined selected health care visits that occurred 1-6 months before ovarian cancer diagnosis. We used multivariable-adjusted logistic regression to estimate odds ratios (ORs) and 95% CIs for associations of sociodemographic factors with number of prediagnostic visits and number of visits with tumor characteristics, and Cox proportional hazards regression to examine differences in survival by number of visits. Results: Women with >5 vs 0 prediagnostic visits were statistically significantly less likely to be diagnosed with distant vs local stage disease (OR, 0.72; 95% CI, 0.54-0.96), and women with 3-5 or >5 vs 0 prediagnostic visits had better overall survival (hazard ratio [HR], 0.88; 95% CI, 0.80-0.96 and HR, 0.90; 95% CI, 0.83-0.98, respectively). In stratified analyses, the association with improved survival was observed only among cases with regional or distant stage disease. Conclusions: Women with high health care utilization prior to ovarian cancer diagnosis may have better prognosis and survival, possibly because of earlier detection or better access to care throughout treatment. Women and their health care providers should not ignore symptoms potentially indicative of ovarian cancer and should be persistent in following up on symptoms that do not resolve.

Surgeon and Hospital Factors Associated With Outcomes in the New York State Database.

INTRODUCTION: We sought to explore the relationship between various surgeon-related and hospital-level characteristics and clinical outcomes among patients requiring cardiac surgery. METHODS: We searched the New York State Cardiac Data Reporting System for all coronary artery bypass grafting (CABG) and valve cases between 2015 and 2017. The data were analyzed without dichotomization. RESULTS: Among CABG/valve surgeons, case volume was positively correlated with years in practice (P = 0.002) and negatively correlated with risk-adjusted mortality ratio (P = 0.014). For CABG and CABG/valve surgeons, our results showed a negative association between teaching status and case volume (P = 0.002, P = 0.018). Among CABG surgeons, hospital teaching status and presence of cardiothoracic surgery residency were inversely associated with risk-adjusted mortality ratio (P = 0.006, P = 0.029). CONCLUSIONS: There is a complex relationship between case volume, teaching status, and surgical outcomes suggesting that balance between academics and volume is needed.

TRPV4-Expressing Tissue-Resident Macrophages Regulate the Function of Collecting Lymphatic Vessels via Thromboxane A2 Receptors in Lymphatic Muscle Cells.

Rationale: TRPV4 channels are critical regulators of blood vascular function and have been shown to be dysregulated in many disease conditions in association with inflammation and tissue fibrosis. These are key features in the pathophysiology of lymphatic system diseases, including lymphedema and lipedema; however, the role of TRPV4 channels in the lymphatic system remains largely unexplored. TRPV4 channels are calcium permeable, non-selective cation channels that are activated by diverse stimuli, including shear stress, stretch, temperature, and cell metabolites, which may regulate lymphatic contractile function. Objective: To characterize the expression of TRPV4 channels in collecting lymphatic vessels and to determine the extent to which these channels regulate the contractile function of lymphatics. Methods and Results: Pressure myography on intact, isolated, and cannulated lymphatic vessels showed that pharmacological activation of TRPV4 channels with GSK1016790A (GSK101) led to contractile dysregulation. The response to GSK101 was multiphasic and included, 1) initial robust constriction that was sustained for ≥1 minute and in some instances remained for ≥4 minutes; and 2) subsequent vasodilation and partial or complete inhibition of lymphatic contractions associated with release of nitric oxide. The functional response to activation of TRPV4 channels displayed differences across lymphatics from four anatomical regions, but these differences were consistent across different species (mouse, rat, and non-human primate). Importantly, similar responses were observed following activation of TRPV4 channels in arterioles. The initial and sustained constriction was prevented with the COX inhibitor, indomethacin. We generated a controlled and spatially defined single-cell RNA sequencing (scRNAseq) dataset from intact and microdissected collecting lymphatic vessels. Our data uncovered a subset of macrophages displaying the highest expression of Trpv4 compared to other cell types within and surrounding the lymphatic vessel wall. These macrophages displayed a transcriptomic profile consistent with that of tissue-resident macrophages (TRMs), including differential expression of Lyve1 , Cd163 , Folr2 , Mrc1 , Ccl8 , Apoe , Cd209f , Cd209d , and Cd209g ; and at least half of these macrophages also expressed Timd4. This subset of macrophages also highly expressed Txa2s , which encodes the thromboxane A2 (TXA2) synthase. Inhibition of TXA2 receptors (TXA2Rs) prevented TRPV4-mediated contractile dysregulation. TXA2R activation on LMCs caused an increase in mobilization of calcium from intracellular stores through Ip3 receptors which promoted store operated calcium entry and vasoconstriction. Conclusions: Clinical studies have linked cancer-related lymphedema with an increased infiltration of macrophages. While these macrophages have known anti-inflammatory and pro-lymphangiogenic roles, as well as promote tissue repair, our results point to detrimental effects to the pumping capacity of collecting lymphatic vessels mediated by activation of TRPV4 channels in macrophages. Pharmacological targeting of TRPV4 channels in LYVE1-expressing macrophages or pharmacological targeting of TXA2Rs may offer novel therapeutic strategies to improve lymphatic pumping function and lymph transport in lymphedema.

TRIM46 is not required for axon specification or axon initial segment formation in vivo.

Vertebrate nervous systems use the axon initial segment (AIS) to initiate action potentials and maintain neuronal polarity. The microtubule-associated protein tripartite motif containing 46 (TRIM46) was reported to regulate axon specification, AIS assembly, and neuronal polarity through the bundling of microtubules in the proximal axon. However, these claims are based on TRIM46 knockdown in cultured neurons. To investigate TRIM46 function in vivo , we examined TRIM46 knockout mice. Contrary to previous reports, we find that TRIM46 is dispensable for AIS formation and maintenance, and axon specification. TRIM46 knockout mice are viable, have normal behavior, and have normal brain structure. Thus, TRIM46 is not required for AIS formation, axon specification, or nervous system function. We also show TRIM46 enrichment in the first ∼100 µm of axon occurs independently of ankyrinG (AnkG), although AnkG is required to restrict TRIM46 only to the AIS. Our results suggest an unidentified protein may compensate for loss of TRIM46 in vivo and highlight the need for further investigation of the mechanisms by which the AIS and microtubules interact to shape neuronal structure and function. SIGNIFICANCE STATEMENT: A healthy nervous system requires the polarization of neurons into structurally and functionally distinct compartments, which depends on both the axon initial segment (AIS) and the microtubule cytoskeleton. In contrast to previous reports, we show that the microtubule-associated protein TRIM46 is not required for axon specification or AIS formation in mice. Our results emphasize the need for further investigation of the mechanisms by which the AIS and microtubules interact to shape neuronal structure and function.

Life at the crossroads: the nuclear LINC complex and vascular mechanotransduction.

Vascular endothelial cells line the inner surface of all blood vessels, where they are exposed to polarized mechanical forces throughout their lifespan. Both basal substrate interactions and apical blood flow-induced shear stress regulate blood vessel development, remodeling, and maintenance of vascular homeostasis. Disruption of these interactions leads to dysfunction and vascular pathologies, although how forces are sensed and integrated to affect endothelial cell behaviors is incompletely understood. Recently the endothelial cell nucleus has emerged as a prominent force-transducing organelle that participates in vascular mechanotransduction, via communication to and from cell-cell and cell-matrix junctions. The LINC complex, composed of SUN and nesprin proteins, spans the nuclear membranes and connects the nuclear lamina, the nuclear envelope, and the cytoskeleton. Here we review LINC complex involvement in endothelial cell mechanotransduction, describe unique and overlapping functions of each LINC complex component, and consider emerging evidence that two major SUN proteins, SUN1 and SUN2, orchestrate a complex interplay that extends outward to cell-cell and cell-matrix junctions and inward to interactions within the nucleus and chromatin. We discuss these findings in relation to vascular pathologies such as Hutchinson-Gilford progeria syndrome, a premature aging disorder with cardiovascular impairment. More knowledge of LINC complex regulation and function will help to understand how the nucleus participates in endothelial cell force sensing and how dysfunction leads to cardiovascular disease.

Evolution of Telehealth Program to Meet Current Needs of Post-Acute and Long-Term Care Communities.

This article describes a telehealth program initially created to reduce transfers to acute care from the nursing home and its evolution into a robust program that includes Behavioral Health, a Medical Director program, and telenursing.

Can DNA methylation shape climate response in trees?

Woody plants create the ecosystems they occupy and shape their biodiversity. Today's rapidly warming climate threatens these long-lived species by creating new environments in which existing populations become maladapted. Plants show enormous phenotypic diversity in response to environmental change, which can be caused by genotype or epigenetic mechanisms that influence the expression of the underlying DNA sequence. Whether epigenetics can affect ecologically important traits in trees is an important and controversial question. We explore the evidence that DNA methylation can affect gene expression, both directly and indirectly via its interaction with transposable elements (TEs), and subsequently shapes phenotypic variation in natural tree populations. Furthermore, we consider the potential of epigenetic approaches to assist in their conservation management strategies.