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1.
JAMA Health Forum ; 5(7): e241756, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967949

ABSTRACT

Importance: Medicare provides nearly universal insurance coverage at age 65 years. However, how Medicare eligibility affects disparities in health insurance coverage, access to care, and health status among individuals by sexual orientation and gender identity is poorly understood. Objective: To assess the association of Medicare eligibility with disparities in health insurance coverage, access to care, and self-reported health status among individuals by sexual orientation and by gender identity. Design, Setting, and Participants: This cross-sectional study used the age discontinuity for Medicare eligibility at age 65 years to isolate the association of Medicare with health insurance coverage, access to care, and self-reported health status, by their sexual orientation and by their gender identity. Data were collected from the Behavioral Risk Factor Surveillance System for respondents from 51 to 79 years old from 2014 to 2021. Data analysis was performed from September 2022 to April 2023. Exposures: Medicare eligibility at age 65 years. Main Outcomes and Measures: Proportions of respondents with health insurance coverage, usual source of care, cost barriers to care, influenza vaccination, and self-reported health status. Results: The study population included 927 952 individuals (mean [SD] age, 64.4 [7.7] years; 524 972 [56.6%] females and 402 670 [43.4%] males), of whom 28 077 (3.03%) identified as a sexual minority-lesbian, gay, bisexual, or another sexual minority identity (LGB+) and 3286 (0.35%) as transgender or gender diverse. Respondents who identified as heterosexual had greater improvements at age 65 years in insurance coverage (4.2 percentage points [pp]; 95% CI, 4.0-4.4 pp) than those who identified as LGB+ (3.6 pp; 95% CI, 2.3-4.8 pp), except when the analysis was limited to a subsample of married respondents. For access to care, improvements in usual source of care, cost barriers to care, and influenza vaccination were larger at age 65 years for heterosexual respondents compared with LGB+ respondents, although confidence intervals were overlapping and less precise for LGB+ individuals. For self-reported health status, the analyses found larger improvements at age 65 years for LGB+ respondents compared with heterosexual respondents. There was considerable heterogeneity by state in disparities by sexual orientation among individuals who were nearly eligible for Medicare (close to 65 years old), with the US South and Central states demonstrating the highest disparities. Among the top-10 highest-disparities states, Medicare eligibility was associated with greater increases in coverage (6.7 pp vs 5.0 pp) and access to a usual source of care (1.4 pp vs 0.6 pp) for LGB+ respondents compared with heterosexual respondents. Conclusions and Relevance: The findings of this cross-sectional study indicate that Medicare eligibility was not associated with consistently greater improvements in health insurance coverage and access to care among LGBTQI+ individuals compared with heterosexual and/or cisgender individuals. However, among sexual minority individuals, Medicare may be associated with closing gaps in self-reported health status, and among states with the highest disparities, it may improve health insurance coverage, access to care, and self-reported health status.


Subject(s)
Eligibility Determination , Health Services Accessibility , Medicare , Humans , United States , Male , Female , Aged , Health Services Accessibility/economics , Health Services Accessibility/statistics & numerical data , Cross-Sectional Studies , Medicare/economics , Medicare/statistics & numerical data , Middle Aged , Gender Identity , Insurance Coverage/statistics & numerical data , Health Status , Sexual and Gender Minorities/statistics & numerical data , Sexual Behavior , Healthcare Disparities/economics , Healthcare Disparities/statistics & numerical data , Behavioral Risk Factor Surveillance System
2.
New Phytol ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38952028

ABSTRACT

Plant homeodomain leucine zipper IV (HD-Zip IV) transcription factors (TFs) contain an evolutionarily conserved steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain. While the START domain is required for TF activity, its presumed role as a lipid sensor is not clear. Here we used tandem affinity purification from Arabidopsis cell cultures to demonstrate that PROTODERMAL FACTOR2 (PDF2), a representative member that controls epidermal differentiation, recruits lysophosphatidylcholines (LysoPCs) in a START-dependent manner. Microscale thermophoresis assays confirmed that a missense mutation in a predicted ligand contact site reduces lysophospholipid binding. We additionally found that PDF2 acts as a transcriptional regulator of phospholipid- and phosphate (Pi) starvation-related genes and binds to a palindromic octamer with consensus to a Pi response element. Phospholipid homeostasis and elongation growth were altered in pdf2 mutants according to Pi availability. Cycloheximide chase experiments revealed a role for START in maintaining protein levels, and Pi starvation resulted in enhanced protein destabilization, suggesting a mechanism by which lipid binding controls TF activity. We propose that the START domain serves as a molecular sensor for membrane phospholipid status in the epidermis. Our data provide insights toward understanding how the lipid metabolome integrates Pi availability with gene expression.

3.
Adv Sci (Weinh) ; : e2402385, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38965931

ABSTRACT

Polymerization in the solid state is generally infeasible due to restrictions on mobility. However, in this work, the solid-state photopolymerization of crystalline dicyclopentadiene is demonstrated via photoinitiated ring-opening metathesis polymerization. The source of mobility in the solid state is attributed to the plastic crystal nature of dicyclopentadiene, which yields local short-range mobility due to orientational degrees of freedom. Polymerization in the solid state enables photopatterning, volumetric additive manufacturing of free-standing structures, and fabrication with embedded components. Solid-state photopolymerization of dicyclopentadiene offers a new paradigm for advanced and freeform fabrication of high-performance thermosets.

4.
Molecules ; 29(11)2024 May 22.
Article in English | MEDLINE | ID: mdl-38893312

ABSTRACT

Gain-of-function mutations in the KCNT1 gene, which encodes the sodium-activated potassium channel known as SLACK, are associated with the rare but devastating developmental and epileptic encephalopathy known as epilepsy of infancy with migrating focal seizures (EIMFS). The design of small molecule inhibitors of SLACK channels represents a potential therapeutic approach to the treatment of EIMFS, other childhood epilepsies, and developmental disorders. Herein, we describe a hit optimization effort centered on a xanthine SLACK inhibitor (8) discovered via a high-throughput screen. Across three distinct regions of the chemotype, we synthesized 58 new analogs and tested each one in a whole-cell automated patch-clamp assay to develop structure-activity relationships for inhibition of SLACK channels. We further evaluated selected analogs for their selectivity versus a variety of other ion channels and for their activity versus clinically relevant SLACK mutants. Selectivity within the series was quite good, including versus hERG. Analog 80 (VU0948578) was a potent inhibitor of WT, A934T, and G288S SLACK, with IC50 values between 0.59 and 0.71 µM across these variants. VU0948578 represents a useful in vitro tool compound from a chemotype that is distinct from previously reported small molecule inhibitors of SLACK channels.


Subject(s)
Potassium Channel Blockers , Structure-Activity Relationship , Humans , Potassium Channel Blockers/chemistry , Potassium Channel Blockers/pharmacology , Potassium Channels, Sodium-Activated , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Xanthine/chemistry , Xanthine/pharmacology , Patch-Clamp Techniques , HEK293 Cells , Molecular Structure , Xanthines/chemistry , Xanthines/pharmacology
5.
bioRxiv ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38895482

ABSTRACT

Rearrangements between genes can yield neomorphic fusions that drive oncogenesis. Fusion oncogenes are made up of fractional segments of the partner genes that comprise them, with each partner potentially contributing some of its own function to the nascent fusion oncoprotein. Clinically, fusion oncoproteins driving one diagnostic entity are typically clustered into a single molecular subset and are often treated a similar fashion. However, knowledge of where specific fusion breakpoints occur in partner genes, and the resulting retention of functional domains in the fusion, is an important determinant of fusion oncoprotein activity and may differ between patients. This study investigates this phenomena through the example of CIC::DUX4, a fusion between the transcriptional repressor capicua (CIC) and the double homeobox 4 gene (DUX4), which drives an aggressive subset of undifferentiated round cell sarcoma. Using a harmonized dataset of over 100 patient fusion breakpoints from the literature, we show that most bona fide CIC::DUX4 fusions retain the C1 domain, which is known to contribute to DNA binding by wild type CIC. Mechanistically, deletion or mutation of the C1 domain reduces, but does not eliminate, activation of CIC target genes by CIC::DUX4. We also find that expression of C1-deleted CIC::DUX4 is capable of exerting intermediate transformation-related phenotypes compared with those imparted by full-length CIC::DUX4, but was not sufficient for tumorigenesis in a subcutaneous mouse model. In summary, our results suggest a supercharging role for the C1 domain in the activity of CIC::DUX4.

6.
Nat Commun ; 15(1): 5434, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38937454

ABSTRACT

Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.


Subject(s)
Diet, High-Fat , Inflammation , Intra-Abdominal Fat , Neutrophils , Obesity , Intra-Abdominal Fat/immunology , Intra-Abdominal Fat/metabolism , Animals , Obesity/microbiology , Obesity/immunology , Humans , Neutrophils/immunology , Diet, High-Fat/adverse effects , Mice , Inflammation/immunology , Inflammation/microbiology , Inflammation/pathology , Gastrointestinal Microbiome/immunology , Male , Mice, Inbred C57BL , Female , Feces/microbiology , Microbiota/immunology , Th1 Cells/immunology , Neutrophil Infiltration
7.
Am J Hosp Palliat Care ; : 10499091241263016, 2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38881044

ABSTRACT

BACKGROUND: Caregivers of cancer patients are at increased risk of depression and other health challenges. There is limited understanding of the role of the caregiver's own family members in promoting or discouraging mental wellbeing. Family functioning conceptualizes how family members interact to promote a positive family environment and has the potential to impact caregiver mental health. The purpose of this study is to assess the association between family interactions and depressive symptoms among family caregivers of cancer patients. METHODS: Secondary analysis of baseline data from an NIH-funded randomized control trial of family caregivers of cancer patients recruited from academic palliative care clinics at three sites (2 Midwest, 1 East). We tested for an association between caregiver responses to the Family Quality of Life in Dementia-Family Interactions Subscale and Patient-Reported Outcomes Measurement Information System Depression Short Form 8A using a block-wise approach to linear modeling. RESULTS: A total of 246 caregivers were included in analysis; caregivers were mostly White (82%), not Hispanic or Latina/o (96%), and female (65%), with an average age of 55 years. Overall, participants had high family interactions (mean 57.7, sd 11.7) and an average depressive symptom burden (t-score 52.4, SD 8.57). Family interactions was significantly negatively associated with depressive symptoms (b = -.163, se = .057) when accounting for relevant covariates. CONCLUSION: Family caregivers with more positive family interactions are likely to have fewer depressive symptoms, suggesting family functioning may play a key role in bolstering family caregiver mental health and wellbeing.

8.
Islets ; 16(1): 2361996, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38833523

ABSTRACT

Epidemiological studies consistently link environmental toxicant exposure with increased Type 2 diabetes risk. Our study investigated the diabetogenic effects of a widely used flame retardant, Dechlorane Plus (DP), on pancreatic ß-cells using rodent and human model systems. We first examined pancreas tissues from male mice exposed daily to oral gavage of either vehicle (corn oil) or DP (10, 100, or 1000 µg/kg per day) and fed chow or high fat diet for 28-days in vivo. DP exposure did not affect islet size or endocrine cell composition in either diet group. Next, we assessed the effect of 48-hour exposure to vehicle (DMSO) or DP (1, 10, or 100 nM) in vitro using immortalized rat ß-cells (INS-1 832/3), primary mouse and human islets, and human stem-cell derived islet-like cells (SC-islets). In INS-1 832/3 cells, DP did not impact glucose-stimulated insulin secretion (GSIS) but significantly decreased intracellular insulin content. DP had no effect on GSIS in mouse islets or SC-islets but had variable effects on GSIS in human islets depending on the donor. DP alone did not affect insulin content in mouse islets, human islets, or SC-islets, but mouse islets co-exposed to DP and glucolipotoxic (GLT) stress conditions (28.7 mM glucose + 0.5 mM palmitate) had reduced insulin content compared to control conditions. Co-exposure of mouse islets to DP + GLT amplified the upregulation of Slc30a8 compared to GLT alone. Our study highlights the importance and challenges of using different in vitro models for studying chemical toxicity.


Subject(s)
Hydrocarbons, Chlorinated , Insulin-Secreting Cells , Polycyclic Compounds , Animals , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Humans , Mice , Male , Polycyclic Compounds/pharmacology , Hydrocarbons, Chlorinated/toxicity , Rats , Insulin/metabolism , Flame Retardants/toxicity , Insulin Secretion/drug effects , Mice, Inbred C57BL , Cells, Cultured
9.
ACS ES T Eng ; 4(6): 1492-1506, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38899163

ABSTRACT

As water treatment technology has improved, the amount of available process data has substantially increased, making real-time, data-driven fault detection a reality. One shortcoming of the fault detection literature is that methods are usually evaluated by comparing their performance on hand-picked, short-term case studies, which yields no insight into long-term performance. In this work, we first evaluate multiple statistical and machine learning approaches for detrending process data. Then, we evaluate the performance of a PCA-based fault detection approach, applied to the detrended data, to monitor influent water quality, filtrate quality, and membrane fouling of an ultrafiltration membrane system for indirect potable reuse. Based on two short case studies, the adaptive lasso detrending method is selected, and the performance of the multivariate approach is evaluated over more than a year. The method is tested for different sets of three critical tuning parameters, and we find that for long-term, autonomous monitoring to be successful, these parameters should be carefully evaluated. However, in comparison with industry standards of simpler, univariate monitoring or daily pressure decay tests, multivariate monitoring produces substantial benefits in long-term testing.

10.
Support Care Cancer ; 32(7): 404, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833189

ABSTRACT

PURPOSE: Family caregivers of patients with cancer often experience both loneliness and symptoms of psychological distress, such as anxiety and depression. The purpose of this study was to evaluate the associations between loneliness and anxiety and loneliness and depression among family caregivers of patients with cancer and to investigate whether positive aspects of caregiving can have a moderating effect on these relationships. METHODS: We conducted a cross-sectional exploratory study using baseline data from an ongoing multisite clinical trial. Multiple linear regression models were used to analyze the relationships between loneliness and psychological distress symptoms and the moderating effect of positive aspects of caregiving. Psychological distress outcomes were measured using PROMIS Short Forms (8a) for Anxiety and Depression. RESULTS: We identified a significant association between loneliness and symptoms of both anxiety and depression. Positive aspects of caregiving did not significantly moderate the relationship between loneliness and depression or loneliness and anxiety. CONCLUSION: The results of this study shed new light on the relationship between loneliness and symptoms of psychological distress experienced by family caregivers of cancer patients, providing a better understanding of the impact that recognition of positive aspects of caregiving has on the association between loneliness and psychological distress symptoms. Our findings emphasize the importance of targeting family caregiver loneliness in order to reduce psychological distress among family caregivers of cancer patients.


Subject(s)
Anxiety , Caregivers , Depression , Loneliness , Neoplasms , Psychological Distress , Humans , Loneliness/psychology , Caregivers/psychology , Male , Female , Neoplasms/psychology , Cross-Sectional Studies , Middle Aged , Depression/etiology , Anxiety/etiology , Aged , Adult , Stress, Psychological/etiology , Linear Models
11.
Alzheimers Dement (Amst) ; 16(2): e12598, 2024.
Article in English | MEDLINE | ID: mdl-38903149

ABSTRACT

INTRODUCTION: In observational studies, the association between alcohol consumption and dementia is mixed. METHODS: We performed two-sample Mendelian randomization (MR) using summary statistics from genome-wide association studies of weekly alcohol consumption and late-onset Alzheimer's disease and one-sample MR in the Health and Retirement Study (HRS), wave 2012. Inverse variance weighted two-stage regression provided odds ratios of association between alcohol exposure and dementia or cognitively impaired, non-dementia relative to cognitively normal. RESULTS: Alcohol consumption was not associated with late-onset Alzheimer's disease using two-sample MR (odds ratio [OR] = 1.15, 95% confidence interval [CI]: [0.78, 1.72]). In HRS, doubling weekly alcohol consumption was not associated with dementia (African ancestries, n = 1,322, OR = 1.00, 95% CI [0.45, 2.25]; European ancestries, n = 7,160, OR = 1.37, 95% CI [0.53, 3.51]) or cognitively impaired, non-dementia (African ancestries, n = 1,322, OR = 1.17, 95% CI [0.69, 1.98]; European ancestries, n = 7,160, OR = 0.75, 95% CI [0.47, 1.22]). DISCUSSION: Alcohol consumption was not associated with cognitively impaired, non-dementia or dementia status. Highlights: Cross-sectionally in a large, diverse sample, alcohol appears protective for dementia.We apply two- and one-sample Mendelian randomization to test inferred causality.Mendelian randomization approaches show no association with alcohol and dementia.We conclude that alcohol consumption should not be considered protective.

12.
Phys Rev Lett ; 132(20): 202701, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38829093

ABSTRACT

New astronomical observations point to a nucleosynthesis picture that goes beyond what was accepted until recently. The intermediate "i" process was proposed as a plausible scenario to explain some of the unusual abundance patterns observed in metal-poor stars. The most important nuclear physics properties entering i-process calculations are the neutron-capture cross sections and they are almost exclusively not known experimentally. Here we provide the first experimental constraints on the ^{139}Ba(n,γ)^{140}Ba reaction rate, which is the dominant source of uncertainty for the production of lanthanum, a key indicator of i-process conditions. This is an important step towards identifying the exact astrophysical site of stars carrying the i-process signature.

13.
J Am Chem Soc ; 146(23): 15779-15786, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38804885

ABSTRACT

Utopia Point Bayesian Optimization (UPBO) was used to identify reaction conditions that are highly selective for the formation of N1 and N2-methyl-3-aryl pyrazole constitutional isomers. UPBO was used to explore a wide chemical space and identify basic reaction conditions for a typically acid-catalyzed Knorr pyrazole condensation. These studies revealed that selectivity in the reaction stems from a condition-dependent equilibrium of intermediates prior to dehydration. For the N2-methyl isomer reaction pathway, a hemiaminal intermediate was found to form reversibly under the reaction conditions, enabling a highly selective synthesis of the N2 isomer upon dehydrative workup. UPBO was able to successfully optimize conversion and selectivity simultaneously with search spaces of >1 million potential variable combinations without the need for high-performance computational resources.

14.
Sci Total Environ ; 940: 173361, 2024 Aug 25.
Article in English | MEDLINE | ID: mdl-38777060

ABSTRACT

Per- and polyfluoroalkyl substances (PFAS) enter surface waters from various sources such as wastewater treatment plants, fire-fighting sites, and PFAS-producing and PFAS-using industries. The Las Vegas Wash in Southern Nevada of the United States (U.S.) conveys wastewater effluent from the Las Vegas metropolitan area to Lake Mead, a drinking water source for millions of people in the U.S. Southwest. PFAS have previously been detected in the Las Vegas Wash, but PFAS sources were not identified. In this study, upstream wash tributaries, wastewater treatment effluents, and shallow groundwater wells were sampled in multiple campaigns during dry-weather conditions to investigate possible PFAS sources. Out of 19 PFAS, two short-chain PFAS-perfluoropentanoic acid (48 % of the total molar concentration) and perfluorohexanoic acid (32 %)-comprised the majority of PFAS loading measured in the Las Vegas Wash, followed by perfluorooctanoic acid (9 %). On a mass loading basis, the majority of total measured PFAS (approximately 90 %) and at least 48 % of each specific PFAS in the Las Vegas Wash likely entered via municipal wastewater effluents, of which the main source was likely residential wastewater. One of the drainage areas with a major civilian airport was identified as a potential source of relatively enriched perfluorosulfonic acids to a small wash tributary and shallow groundwater samples. Nonetheless, that tributary contributed at most 15 % of any specific PFAS to the mainstem of the Las Vegas Wash. Total PFAS concentrations were relatively low for the small tributary associated with an urban smaller airport and the lack of flow in the tributary channel immediately downgradient of an Air Force base indicates the smaller airport and base were unlikely significant PFAS sources to the Las Vegas Wash. Overall, this study demonstrated effective PFAS source investigation methodology and the importance of wastewater effluent as a PFAS environmental pathway.

15.
J Spec Oper Med ; 24(2): 78-80, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38788225

ABSTRACT

Needle decompression is a mainstay intervention for tension pneumothorax in trauma medicine. It is used in combat and prehospital medicine when definitive measures are often not available or ideal. It can temporarily relieve increased intrathoracic pressure and treat a collapsed lung or great vessel obstruction. However, when done incorrectly, it can result in underlying visceral organ and vessel trauma. This is a case of an adult male who presented to the emergency department after sustaining multiple stab wounds during an altercation. On arrival, the patient had a 14-gauge angiocatheter inserted at the 4th intercostal space (ICS), left of the parasternal line traversing the right ventricle and interventricular septum and terminating in the left ventricle. The case emphasizes the importance of understanding the landmarks of performing needle decompression in increasing the procedure's efficacy and reducing iatrogenic complications.


Subject(s)
Decompression, Surgical , Emergency Medical Services , Heart Injuries , Needles , Pneumothorax , Wounds, Stab , Humans , Male , Decompression, Surgical/methods , Wounds, Stab/surgery , Wounds, Stab/complications , Heart Injuries/surgery , Heart Injuries/diagnosis , Heart Injuries/etiology , Pneumothorax/etiology , Pneumothorax/surgery , Pneumothorax/therapy , Adult
16.
Urol Pract ; 11(4): 654-660, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38758183

ABSTRACT

INTRODUCTION: We sought to determine if work relative value unit differences exist between analogous, sex-specific procedures. METHODS: Representatives from the AUA and the American College of Obstetricians and Gynecologists independently reviewed the entire procedural code set and identified sex-specific procedures that had an analogous procedure in the opposite sex. These pairs were then evaluated and compared using current American Medical Association Relative Value Scale Update Committee methodology. Comparable code pair values were then examined to determine any systemic bias in the work relative value units assigned between the procedures. Mean differences and 95% confidence intervals were used to determine any differences in procedure or physician time values. The methodology used considered global period, intraservice time, total time, hospital days, postoperative office visits, and the date of the committee review. RESULTS: Of the 10 directly analogous code pairs reviewed, 7 of the female procedures had higher work relative value unit differences (range 0.29-6.47), and 3 of the male procedures had higher work relative value unit differences (range 1.23-2.34). There was no statistical difference between the code pair work relative value units. The work relative value unit per minute of intraservice time and total time were not statistically different. CONCLUSIONS: In this study, we compared operative procedures performed in women with clinically comparable operative procedures performed in men that had similar surgical approaches, global periods, and valuation methodologies. Overall, no statistical differences in work relative value units were demonstrated.


Subject(s)
Gynecologic Surgical Procedures , Relative Value Scales , Urologic Surgical Procedures , Humans , Female , Male , Urologic Surgical Procedures/statistics & numerical data , United States
17.
Am J Emerg Med ; 81: 130-135, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38728935

ABSTRACT

BACKGROUND: Gallbladder distention has been described in radiology literature but its value on point-of-care ultrasound (PoCUS) performed by emergency physicians is unclear. We sought to determine the test characteristics of gallbladder distention on PoCUS for cholecystitis (acute or chronic), and secondarily whether distention was associated with an obstructing stone-in-neck (SIN), acute cholecystitis on subsequent pathology report, and longer cholecystectomy operative times. METHODS: This was a dual-site retrospective cohort study of all Emergency Department (ED) patients that underwent diagnostic biliary PoCUS and were subsequently admitted from 11/1/2020 to 10/31/2022. Patients with pregnancy, liver failure, ascites, hepatobiliary cancer, prior cholecystectomy, or known cholecystitis were excluded. Gallbladder distention was defined as a width ≥4 cm or a length ≥10 cm. Saved ultrasound images were reviewed by three independent reviewers who obtained measurements during the review. Test characteristics, Cohen's kappa (κ), and strength of association between distention and our variables (acute cholecystitis on pathology report and SIN on PoCUS) were calculated using a Chi Square analysis, where intervention (cholecystectomy, percutaneous cholecystostomy, or intravenous antibiotics) was used as the reference standard for AC. A one-tail two sample t-test was calculated for mean operative times. RESULTS: Of 280 admitted patients who underwent ED biliary PoCUS, 53 were excluded, and 227 were analyzed. Of the 227 patients, 113 (49.8%) had cholecystitis according to our reference standard, and 68 (30.0%) had distention on PoCUS: 32 distended by both width and length, 16 distended by width alone, and 20 distended by length alone. Agreement between investigators was substantial for width (κ 0.630) and length (κ 0.676). Distention was 85.09% (95% CI 77.20-91.07%) specific and 45.1% (95% CI 35.8-54.8%) sensitive for cholecystitis. There was an association between distention and SIN; odds ratio (OR) 2.76 (95% CI 1.54-4.97). Distention of both length and width was associated with acute over chronic cholecystitis; OR 4.32 (95% CI 1.42-13.14). Among patients with acute cholecystitis, mean operative times were 114 min in patients with distention and 89 min in patients without distention (p = 0.03). CONCLUSION: Gallbladder distention on PoCUS was specific for cholecystitis (acute or chronic), and associated with SIN, acute cholecystitis on subsequent pathology report, and longer cholecystectomy operative times. Measurement of gallbladder dimensions as part of the assessment of cholecystitis may be advantageous.


Subject(s)
Cholecystitis, Acute , Ultrasonography , Humans , Cholecystitis, Acute/diagnostic imaging , Cholecystitis, Acute/diagnosis , Female , Retrospective Studies , Male , Middle Aged , Aged , Gallbladder/diagnostic imaging , Gallbladder/pathology , Emergency Service, Hospital , Adult , Cholecystectomy , Point-of-Care Systems , Operative Time
18.
J Proteome Res ; 23(6): 1970-1982, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38718259

ABSTRACT

Lamin A/C (LMNA) is an important component of nuclear lamina. Mutations cause arrhythmia, heart failure, and sudden cardiac death. While LMNA-associated cardiomyopathy typically has an aggressive course that responds poorly to conventional heart failure therapies, there is variability in severity and age of penetrance between and even within specific mutations, which is poorly understood at the cellular level. Further, this heterogeneity has not previously been captured to mimic the heterozygous state, nor have the hundreds of clinical LMNA mutations been represented. Herein, we have overexpressed cardiopathic LMNA variants in HEK cells and utilized state-of-the-art quantitative proteomics to compare the global proteomic profiles of (1) aggregating Q353 K alone, (2) Q353 K coexpressed with WT, (3) aggregating N195 K coexpressed with WT, and (4) nonaggregating E317 K coexpressed with WT to help capture some of the heterogeneity between mutations. We analyzed each data set to obtain the differentially expressed proteins (DEPs) and applied gene ontology (GO) and KEGG pathway analyses. We found a range of 162 to 324 DEPs from over 6000 total protein IDs with differences in GO terms, KEGG pathways, and DEPs important in cardiac function, further highlighting the complexity of cardiac laminopathies. Pathways disrupted by LMNA mutations were validated with redox, autophagy, and apoptosis functional assays in both HEK 293 cells and in induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) for LMNA N195 K. These proteomic profiles expand our repertoire for mutation-specific downstream cellular effects that may become useful as druggable targets for personalized medicine approach for cardiac laminopathies.


Subject(s)
Lamin Type A , Mutation , Proteomics , Lamin Type A/genetics , Lamin Type A/metabolism , Humans , Proteomics/methods , HEK293 Cells , Cardiomyopathies/genetics , Cardiomyopathies/metabolism , Proteome/genetics , Proteome/metabolism , Gene Ontology
19.
Int J Sports Phys Ther ; 19(5): 581-590, 2024.
Article in English | MEDLINE | ID: mdl-38707852

ABSTRACT

Background: Thoracic rotation mobility is crucial for athletes in rotational sports such as baseball, golf, and swimming to maintain the proper biomechanics associated with the sport. Accurate differentiation between normal mobility and active and passive physiological deficits in the thoracic region is critical for identifying the need for intervention to the thorax. Purpose: To establish the reliability and discriminant validity of visual estimation of thorax rotation range of motion across clinicians of differing experience levels in determining normal mobility and active or passive physiological deficits when utilizing the quadruped lumbar-locked position. Study Design: Cross-sectional. Methods: Thirty-eight subjects (21 female, 17 male) with a mean age of 27 years ± 6.67 were assessed with the quadruped lumbar-locked thorax rotation test by three examiners with various clinical experience in real-time and again one week later. Bilateral active and passive lumbar-locked thorax rotation mobility was assessed by all raters and categorized as "Unrestricted" (≥50°) or "Restricted" (<50°) while a research assistant simultaneously measured the motion with a digital inclinometer. All raters were blinded to the results. All results were analyzed for intra-rater reliability and agreement. Results: Test-retest intra-rater reliability ranged from 0.55-0.72 and percent absolute agreement ranged from 0.82-0.89. Inter-rater reliability ranged from 0.45-0.59 while percent absolute agreement between raters ranged from 0.74-0.84. There was a significant difference in range of motion between "Unrestricted" and "Restricted" categories for both active (Unrestricted=54.6-58.9; Restricted=40.4-44.4; p<0.001) and passive motion (Unrestricted=61.3-63.5; Restricted=39.2-39.7; p<0.001). The only interaction effect was for passive left rotation [Rater A Restricted x ® =34.3(30.4-38.2); Rater C Restricted (x ) ®=43.8(41.3-46.4); p=.000]. Conclusion: The quadruped lumbar-locked thorax rotation test demonstrates moderate to substantial test-retest intra-rater and inter-rater reliability regardless of clinical experience. The quadruped lumbar-locked thorax rotation test can accurately discriminate between individuals with active and passive physiological deficits regardless of rater experience using visual estimation. Level of Evidence: 3b.

20.
Article in English | MEDLINE | ID: mdl-38725637

ABSTRACT

We present partial genome sequences of 50 salamander species (Urodela) from 10 genera and 4 families. These span nearly the entire range of genome sizes in salamanders, from ~14-130GB, the latter of which is among the largest of all animal genomes. Only three salamander genomes were available to this point, from Ambystomatidae (one species) and Salamandridae (two species from two genera), to which we have added Amphiumidae (one species), Plethodontidae (45 species from 6 genera), Proteidae (one species), and Sirenidae (three species from two genera). These span ~140 million years of evolutionary divergence, leaving only Cryptobranchidae, Hynobiidae, and Rhyacotritonidae as salamander families without genome assemblies. These data should facilitate additional future work on speciation and genome evolution, both within Urodela and across Animalia.

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