The uneven impact of Medicaid expansion on rural and urban Black, Latino/a, and White mortality.

PURPOSE: To determine the differential impact of Medicaid expansion on all-cause mortality between Black, Latino/a, and White populations in rural and urban areas, and assess how expansion impacted mortality disparities between these groups. METHODS: We employ a county-level time-varying heterogenous treatment effects difference-in-difference analysis of Medicaid expansion on all-cause age-adjusted mortality for those 64 years of age or younger from 2009 to 2019. For all counties within the 50 US States and the District of Columbia, we use restricted-access vital statistics data to estimate Average Treatment Effect on the Treated (ATET) for all combinations of racial and ethnic group (Black, Latino/a, White), rurality (rural, urban), and sex. We then assess aggregate ATET, as well as how the ATET changed as time from expansion increased. FINDINGS: Medicaid expansion led to a reduction in all-cause age-adjusted mortality for urban Black populations, but not rural Black populations. Urban White populations experienced mixed effects dependent on years after expansion. Latino/a populations saw no appreciable impact. While no effect was observed for rural Black and Latino/a populations, rural White all-cause age-adjusted mortality unexpectedly increased due to Medicaid expansion. These effects reduced rural- and urban-specific Black-White mortality disparities but did not shrink the rural-urban mortality gap. CONCLUSIONS: The mortality-reducing impact of Medicaid expansion has been uneven across racial and ethnic groups and rural-urban status; suggesting that many populations-particularly rural individuals-are not seeing the same benefits as others. It is imperative that states work to ensure Medicaid expansion is being appropriately implemented in rural areas.

Correction: Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn's colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease.

[This corrects the article DOI: 10.1371/journal.pone.0246393.].

Podocytopathies associated with familial partial lipodystrophy due to LMNA variants: report of two cases.

Lipodystrophies are characterized by complete or selective loss of adipose tissue and can be acquired or inherited. Familial partial lipodystrophy (FPLD) is a hereditary lipodystrophy commonly caused by mutations in the LMNA gene. Herein, we report two cases of FPLD associated with podocytopathies. Patient 1 was diagnosed with FPLD associated with the heterozygous p.Arg482Trp variant in LMNA and had normal glucose tolerance and hyperinsulinemia. During follow-up, she developed nephroticrange proteinuria. Renal biopsy was consistent with minimal change disease. Patient 2 was diagnosed with FPLD associated with a de novo heterozygous p.Arg349Trp variant in LMNA. Microalbuminuria progressed to macroalbuminuria within 6 years and tonephrotic range proteinuria in the last year. He remained without diabetes and with hyperinsulinemia. Renal biopsy revealed focal segmental glomerulosclerosis not otherwise specified. This report provides further evidence of variable features of lipodystrophy associated with LMNA variants and the importance of long-term follow-up with evaluation of kidney dysfunction.

Neighborhood disadvantage is associated with working memory and hippocampal volumes among older adults.

It is not well understood how neighborhood disadvantage is associated with specific domains of cognitive function and underlying brain health within older adults. Thus, the objective was to examine associations between neighborhood disadvantage, brain health, and cognitive performance, and examine whether associations were more pronounced among women. The study included 136 older adults who underwent cognitive testing and MRI. Neighborhood disadvantage was characterized using the Area Deprivation Index (ADI). Descriptive statistics, bivariate correlations, and multiple regressions were run. Multiple regressions, adjusted for age, sex, education, and depression, showed that higher ADI state rankings (greater disadvantage) were associated with poorer working memory performance (p < .01) and lower hippocampal volumes (p < .01), but not total, frontal, and white matter lesion volumes, nor visual and verbal memory performance. There were no significant sex interactions. Findings suggest that greater neighborhood disadvantage may play a role in working memory and underlying brain structure.

The double life of trichomes: understanding their dual role in herbivory and herbicide resistance.

Understanding the evolutionary forces that maintain phenotypic variation in ecologically relevant traits has long been one of the central goals of evolutionary ecology. While the maintenance of variation in plant defense is most often hypothesized to be due to trait trade-offs or spatiotemporal variation in herbivore abundance, the role that heterogeneous selective agents may play on the maintenance of variation in plant defense is less examined. Trichomes are hair-like appendages on plant surfaces that can defend against multiple damaging agents such as pathogens, herbivores, and UV radiation. It is currently unknown however if conflicting selection from such heterogeneous agents of damage may act to maintain the variation observed in trichome traits. Here, we assess whether trichomes serve as an herbicide resistance trait and how it coincides with the conventionally studied defensive strategy of herbivory resistance. In a series of experiments, we exposed the annual invasive velvetleaf (Abutilon theophrasti) to glyphosate (active ingredient in "Roundup") to investigate whether trichome traits (type and density) are linked to herbicide resistance and to test whether herbicide influences selection on plant trichomes. We found that an increased proportion of branched trichomes positively impacted herbicide resistance and chewing herbivory resistance. We also found evidence that glyphosate imposes positive selection on branched trichomes in velvetleaf. Overall, our results indicate that branched trichomes can contribute to both herbicide and herbivory resistance, serving a concordant rather than conflicting role to reduce plant injury. Our findings further suggest that novel anthropogenic agents of selection can alter the composition of plant defense traits, potentially impacting trait-mediated interactions among external stressors.

Podocytopathies associated with familial partial lipodystrophy due to LMNA variants: report of two cases

SUMMARY Lipodystrophies are characterized by complete or selective loss of adipose tissue and can be acquired or inherited. Familial partial lipodystrophy (FPLD) is a hereditary lipodystrophy commonly caused by mutations in the LMNA gene. Herein, we report two cases of FPLD associated with podocytopathies. Patient 1 was diagnosed with FPLD associated with the heterozygous p.Arg482Trp variant in LMNA and had normal glucose tolerance and hyperinsulinemia. During follow-up, she developed nephrotic-range proteinuria. Renal biopsy was consistent with minimal change disease. Patient 2 was diagnosed with FPLD associated with a de novo heterozygous p.Arg349Trp variant in LMNA. Microalbuminuria progressed to macroalbuminuria within 6 years and to nephrotic range proteinuria in the last year. He remained without diabetes and with hyperinsulinemia. Renal biopsy revealed focal segmental glomerulosclerosis not otherwise specified. This report provides further evidence of variable features of lipodystrophy associated with LMNA variants and the importance of long-term follow-up with evaluation of kidney dysfunction.

Comparative Analysis of Resident Space Object (RSO) Detection Methods.

In recent years, there has been a significant increase in satellite launches, resulting in a proliferation of satellites in our near-Earth space environment. This surge has led to a multitude of resident space objects (RSOs). Thus, detecting RSOs is a crucial element of monitoring these objects and plays an important role in preventing collisions between them. Optical images captured from spacecraft and with ground-based telescopes provide valuable information for RSO detection and identification, thereby enhancing space situational awareness (SSA). However, datasets are not publicly available due to their sensitive nature. This scarcity of data has hindered the development of detection algorithms. In this paper, we present annotated RSO images, which constitute an internally curated dataset obtained from a low-resolution wide-field-of-view imager on a stratospheric balloon. In addition, we examine several frame differencing techniques, namely, adjacent frame differencing, median frame differencing, proximity filtering and tracking, and a streak detection method. These algorithms were applied to annotated images to detect RSOs. The proposed algorithms achieved a competitive degree of success with precision scores of 73%, 95%, 95%, and 100% and F1 scores of 68%, 77%, 82%, and 79%.

Addressing health inequities through simulation training and education in rural and tribal communities.

Background: The nursing shortage is serious and getting worse in medically underserved areas. Nursing education needs to include faculty education in simulation-based education that focuses on public health and cultural education. New nurse graduates are inadequately prepared and need additional training to provide culturally appropriate care to varied and rural populations. Method: This project used simulation-based education and rural clinical placements to enhance the training and education needs of faculty, students and community partners to better address the health care needs of people living in rural and medically underserved areas of the Navajo Nation and northern Arizona. Results: The project increased knowledge and interest among faculty and community partners on simulation-based education as well as positive student learning experiences. Conclusion: Public health and culture can be integrated into simulation-based education. Partnerships with tribal communities can play a valuable role in nursing education.

Patient perceptions of cardiovascular risk, lipid management and statins in type 1 diabetes.

Lipid-lowering reduces cardiovascular risk in type 1 diabetes (T1D), but dyslipidaemia remains under-recognised and under-treated. Through patient surveys, barriers to lipid management in T1D were identified, including lack of awareness of cardiovascular risk and cholesterol levels, preference for managing glycaemia over lipids, preference for lifestyle modification over pharmacotherapy, and statin side-effect concerns.

Stratospheric Night Sky Imaging Payload for Space Situational Awareness (SSA).

Space situational awareness (SSA) refers to collecting, analyzing, and keeping track of detailed knowledge of resident space objects (RSOs) in the space environment. With the rapidly increasing number of objects in space, the need for SSA grows as well. Traditional methods rely heavily on imaging RSOs from large, narrow field-of-view (FOV), ground-based telescopes. This research outlines the technology demonstration payload, Resident Space Object Near-space Astrometric Research (RSONAR)-a star tracker-like, wide FOV camera combined with commercial off-the-shelf (COTS) hardware to image RSOs from the stratosphere, overcoming the disadvantages of ground-based observations. The hardware components and software algorithm are described and evaluated. The eligibility of the payload for SSA is proven by the image processing algorithms, which detect the RSOs in the images captured during flight and the survival of the COTS components in the near-space environment. The payload features a low-resolution, wide FOV camera coupled with a Field Programmable Gate Array (FPGA)-based platform that houses the altitude and time-based image capture algorithm. The newly developed payload in a 2U-CubeSat form factor was flown as a space-ready payload on the CSA/CNES stratospheric balloon research platform to carry out algorithm and functionality tests in August 2022.

Path of fear: Experiences of health professionals in the fight against COVID-19.

This study aimed to understand the expressions of fear in the journeys of health professionals who worked in the confrontation of coronavirus disease 2019 (COVID-19), in the city of Manaus, in the Brazilian Western Amazon. This is an exploratory qualitative study that adopts interpretive description as a method to generate informed knowledge responsive to the needs of the practice. We included 56 participants, comprising 23 health managers and 33 health workers (middle and higher level) of different professional categories. The results revealed three circles of experience: (1) knowledge and professional experience in dealing with the disease (unknown-known-experienced); (2) the growing proximity to death and loss (predicted-witnessed-suffered); and (3) the involvement and proximity to whatever affects the individual, their emotions, and personal transformations in the face of the threat (the collective, the neighbor, and oneself). Our results suggest that health professionals who worked during the COVID-19 pandemic in Manaus experienced insecurity, dread, and fear, illustrating the complexity of developing their activities in the front line of care and management during the different phases of the pandemic. A contribution of the study is precisely that of capturing this complexity, which suggests the impossibility of analyzing fear only in its simple manifestation, or in each circle of experience.

Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis.

Triple-negative breast cancers (TNBC) tend to become invasive and metastatic at early stages in their development. Despite some treatment successes in early-stage localized TNBC, the rate of distant recurrence remains high, and long-term survival outcomes remain poor. In a search for new therapeutic targets for this disease, we observed that elevated expression of the serine/threonine kinase calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) is highly correlated with tumor invasiveness. In validation studies, genetic disruption of CaMKK2 expression or inhibition of its activity with small molecule inhibitors disrupted spontaneous metastatic outgrowth from primary tumors in murine xenograft models of TNBC. High-grade serous ovarian cancer (HGSOC), a high-risk, poor prognosis ovarian cancer subtype, shares many features with TNBC, and CaMKK2 inhibition effectively blocked metastatic progression in a validated xenograft model of this disease. Mechanistically, CaMKK2 increased the expression of the phosphodiesterase PDE1A, which hydrolyzed cyclic guanosine monophosphate (cGMP) to decrease the cGMP-dependent activity of protein kinase G1 (PKG1). Inhibition of PKG1 resulted in decreased phosphorylation of vasodilator-stimulated phosphoprotein (VASP), which in its hypophosphorylated state binds to and regulates F-actin assembly to facilitate cell movement. Together, these findings establish a targetable CaMKK2-PDE1A-PKG1-VASP signaling pathway that controls cancer cell motility and metastasis by impacting the actin cytoskeleton. Furthermore, it identifies CaMKK2 as a potential therapeutic target that can be exploited to restrict tumor invasiveness in patients diagnosed with early-stage TNBC or localized HGSOC. SIGNIFICANCE: CaMKK2 regulates actin cytoskeletal dynamics to promote tumor invasiveness and can be inhibited to suppress metastasis of breast and ovarian cancer, indicating CaMKK2 inhibition as a therapeutic strategy to arrest disease progression.

Not just flowering time: a resurrection approach shows floral attraction traits are changing over time.

Contemporary anthropogenic changes in climate and landscape form a complex set of selective pressures acting on natural systems, yet, in many systems, we lack information about both whether and how organisms may adapt to these changes. In plants, research has focused on climate-induced changes in phenology and the resultant potential for disruption of plant-pollinator interactions, however, there remains a paucity of knowledge regarding how other pollinator-mediated traits may be involved in the adaptive response. Here, we use resurrection experiments to investigate the phenotypic basis of adaptation in a mixed-mating system plant, the common morning glory (Ipomoea purpurea). Specifically, we measure temporal and spatial changes in traits grouped into three categories relevant to plant-pollinator interactions - floral morphology, floral rewards, and floral phenology. We show a significant temporal increase in corolla size and shift to earlier flowering times, as well as a potential for increased investment in floral rewards, all of which are driven primarily by populations at more northern latitudes. Additionally, we find evidence for directional selection on floral morphology and phenology and evidence of balancing selection acting on anther-stigma distance. Overall, these results show an adaptive response in line with greater investment in pollinator attraction rather than self-pollination and fine-scale spatial differences in adaptive potential.

Families and Friends of Homicide Victims' Experiences With the Healthcare System: A Trauma-Informed Perspective.

INTRODUCTION: Families and friends of homicide victims (FFHV) interact with healthcare systems almost immediately after the traumatic event. Their interactions with healthcare providers can either facilitate healing, have a neutral effect, or compound an already painful experience. When trauma victims are admitted to the hospital, resources are necessarily diverted on their behalf with less consistent attention paid to their families and friends. The interactions surrounding the immediate circumstance as well as experiences in the weeks to months after can have significant long-term impact. This study explores the needs and experiences of FFHV when interacting with the healthcare system to inform physicians' and providers' interactions and provision of services. METHODS: This study of 3 focus groups sought to understand these experiences with the healthcare system to better inform physicians' and providers' interactions and provision of services. RESULTS: Using the framework approach, the study ultimately built upon the existing trauma-informed care (TIC) framework to include several emergent themes. Participants discussed the need for death notification sensitivity, benefits of coordinated care, barriers to accessing care, the need for physician empathy and attention, the lack of trauma screening, and hastily prescribing medications. CONCLUSION: This TIC approach can inform future healthcare interactions with the FFHV as it grounds the patients' experience in their historical reality and may improve future provider-patient relationship.

Preliminary results from a randomized, controlled, cross-over trial of intrathecal oxytocin for neuropathic pain.

OBJECTIVE: Compare intrathecal oxytocin, 100 µg to placebo on ongoing neuropathic pain and mechanical hyperalgesia and allodynia. STUDY DESIGN: Randomized, controlled, double-blind cross-over. SETTING: Clinical research unit. SUBJECTS: Individuals aged 18 to 70 years with neuropathic pain for at least 6 months. METHODS: Individuals received intrathecal injections of oxytocin and saline, separated by at least 7 days, and ongoing pain in neuropathic area (VAS [visual analog scale]) and areas of hypersensitivity to von Frey filament and cotton wisp brushing were measured for 4 hours. Primary outcome was VAS pain in the first 4 hours after injection, analyzed by linear mixed effects model. Secondary outcomes were verbal pain intensity scores at daily intervals for 7 days and areas of hypersensitivity and elicited pain for 4 hours after injections. RESULTS: The study was stopped early after completion of 5 of 40 subjects planned due to slow recruitment and funding limitations. Pain intensity prior to injection was 4.75 ± 0.99 and modeled pain intensity decreased more after oxytocin than placebo to 1.61 ± 0.87 and 2.49 ± 0.87, respectively (P = .003). Daily pain scores were lower in the week following injection of oxytocin than saline (2.53 ± 0.89 vs 3.66 ± 0.89; P = .001). Allodynic area decreased by 11%, but hyperalgesic area increased by 18% after oxytocin compared to placebo. There were no study drug related adverse effects. CONCLUSION: Although limited by the small number of subjects studied, oxytocin reduced pain more than placebo in all subjects. Further study of spinal oxytocin in this population is warranted. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov on 03/27/2014 (NCT02100956). The first subject was studied on 06/25/2014.

Dynamic transcriptomic responses to divergent acute exercise stimuli in young adults.

Acute exercise elicits dynamic transcriptional changes that, when repeated, form the fundamental basis of health, resilience, and performance adaptations. While moderate-intensity endurance training combined with conventional resistance training (traditional, TRAD) is often prescribed and recommended by public health guidance, high-intensity training combining maximal-effort intervals with intensive, limited-rest resistance training is a time-efficient alternative that may be used tactically (HITT) to confer similar benefits. Mechanisms of action of these distinct stimuli are incompletely characterized and have not been directly compared. We assessed transcriptome-wide responses in skeletal muscle and circulating extracellular vesicles (EVs) to a single exercise bout in young adults randomized to TRAD (n = 21, 12 M/9 F, 22 ± 3 yr) or HITT (n = 19, 11 M/8 F, 22 ± 2 yr). Next-generation sequencing captured small, long, and circular RNA in muscle and EVs. Analysis identified differentially expressed transcripts (|log2FC|>1, FDR ≤ 0.05) immediately (h0, EVs only), h3, and h24 postexercise within and between exercise protocols. In aaddition, all apparently responsive transcripts (FDR < 0.2) underwent singular value decomposition to summarize data structures into latent variables (LVs) to deconvolve molecular expression circuits and interregulatory relationships. LVs were compared across time and exercise protocol. TRAD, a longer but less intense stimulus, generally elicited a stronger transcriptional response than HITT, but considerable overlap and key differences existed. Findings reveal shared and unique molecular responses to the exercise stimuli and lay groundwork toward establishing relationships between protein-coding genes and lesser-understood transcripts that serve regulatory roles following exercise. Future work should advance the understanding of these circuits and whether they repeat in other populations or following other types of exercise/stress.NEW & NOTEWORTHY We examined small and long transcriptomics in skeletal muscle and serum-derived extracellular vesicles before and after a single exposure to traditional combined exercise (TRAD) and high-intensity tactical training (HITT). Across 40 young adults, we found more consistent protein-coding gene responses to TRAD, whereas HITT elicited differential expression of microRNA enriched in brain regions. Follow-up analysis revealed relationships and temporal dynamics across transcript networks, highlighting potential avenues for research into mechanisms of exercise response and adaptation.

The consequences of synthetic auxin herbicide on plant-herbivore interactions.

Although herbicide drift is a common side effect of herbicide application in agroecosystems, its effects on the ecology and evolution of natural communities are rarely studied. A recent shift to dicamba, a synthetic auxin herbicide known for 'drifting' to nontarget areas, necessitates the examination of drift effects on the plant-insect interactions that drive eco-evo dynamics in weed communities. We review current knowledge of direct effects of synthetic auxin herbicides on plant-insect interactions, focusing on plant herbivory, and discuss potential indirect effects, which are cascading effects on organisms that interact with herbicide-exposed plants. We end by developing a framework for the study of plant-insect interactions given drift, highlighting potential changes to plant developmental timing, resource quantity, quality, and cues.

Interchromosomal linkage disequilibrium and linked fitness cost loci associated with selection for herbicide resistance.

The adaptation of weeds to herbicide is both a significant problem in agriculture and a model of rapid adaptation. However, significant gaps remain in our knowledge of resistance controlled by many loci and the evolutionary factors that influence the maintenance of resistance. Here, using herbicide-resistant populations of the common morning glory (Ipomoea purpurea), we perform a multilevel analysis of the genome and transcriptome to uncover putative loci involved in nontarget-site herbicide resistance (NTSR) and to examine evolutionary forces underlying the maintenance of resistance in natural populations. We found loci involved in herbicide detoxification and stress sensing to be under selection and confirmed that detoxification is responsible for glyphosate (RoundUp) resistance using a functional assay. We identified interchromosomal linkage disequilibrium (ILD) among loci under selection reflecting either historical processes or additive effects leading to the resistance phenotype. We further identified potential fitness cost loci that were strongly linked to resistance alleles, indicating the role of genetic hitchhiking in maintaining the cost. Overall, our work suggests that NTSR glyphosate resistance in I. purpurea is conferred by multiple genes which are potentially maintained through generations via ILD, and that the fitness cost associated with resistance in this species is likely a by-product of genetic hitchhiking.

Hyperphosphorylated Tau in Mesial Temporal Lobe Epilepsy: a Neuropathological and Cognitive Study.

Temporal lobe epilepsy (TLE) often courses with cognitive deficits, but its underlying neuronal basis remains unclear. Confluent data suggest that epilepsy share pathophysiological mechanisms with neurodegenerative diseases. However, as most studies analyze subjects 60 years old and older, it is challenging to rule out that neurodegenerative changes arise from age-related mechanisms rather than epilepsy in these individuals. To fill this gap, we conducted a neuropathological investigation of the hippocampal formation of 22 adults with mesial TLE and 20 age- and sex-matched controls (both younger than 60 years). Moreover, we interrogated the relationship between these neuropathological metrics and cognitive performance. Hippocampal formation extracted from patients with drug-resistant mesial TLE undergoing surgery and postmortem non-sclerotic hippocampal formation of clinically and neuropathologically controls underwent immunohistochemistry against amyloid ß (Aß), hyperphosphorylated tau (p-tau), and TAR DNA-binding protein-43 (TDP-43) proteins, followed by quantitative analysis. Patients underwent a comprehensive neuropsychological evaluation prior to surgery. TLE hippocampi showed a significantly higher burden of p-tau than controls, whereas Aß deposits and abnormal inclusions of TDP-43 were absent in both groups. Patients with hippocampal sclerosis (HS) type 2 had higher immunostaining for p-tau than patients with HS type 1. In addition, p-tau burden was associated with impairment in attention tasks and seizures frequency. In this series of adults younger than 60 years-old, the increase of p-tau burden associated with higher frequency of seizures and attention impairment suggests the involvement of tau pathology as a potential contributor to cognitive deficits in mesial TLE.

Differential Associations Between the Area Deprivation Index and Measures of Physical Health for Older Black Adults.

OBJECTIVES: This study explored the association between place-based characteristics (e.g., neighborhood socioeconomic deprivation) and physical health within older Black adults, a critical gap in the literature as identified by the National Institute on Minority Health and Health Disparities. METHODS: The sample was from Wave 1 data of Baltimore Study of Black Aging: Patterns of Cognitive Aging (N = 450; Mage = 68.34). Variables included the area deprivation index (ADI), objective (e.g., average blood pressure) and subjective (e.g., self-rated health) measures of physical health. Multiple linear regression models were conducted controlling for key sociodemographic characteristics. RESULTS: Participants reporting better self-rated health and less likely to need help with activities of daily living were significantly more likely to be living in more disadvantaged neighborhoods based on national and state ADI, respectively, even after adjusting for covariates. A significant age and ADI interaction revealed better self-rated health was associated with a more disadvantaged neighborhood particularly for individuals ≤66 years. There was no significant association between ADI and objective physical health measures. DISCUSSION: The findings suggest that national- and state-level place-based characteristics should be considered along with individual-level factors, which can enrich the scientific understanding of how neighborhood characteristics relate to varying health indicators among older Black adults.