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Adipose microsomal triglyceride transfer protein deficiency protects against hepatic steatosis by upregulating PPARα activity

Rajan, Sujith; Verano, Michael; Palaia, Thomas; Prakashmurthy, Chandana; Chung, Jay; Islam, Shahidul; Lee, Lili; James, Antonisamy William; Alemán, José O; Goldberg, Ira J; Fisher, Edward A; Hussain, M Mahmood
BACKGROUND & AIM/UNASSIGNED:Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health issue. Identifying factors that prevent hepatic lipid accumulation could inform new MASLD prevention or treatment strategies. We previously demonstrated that adipocyte microsomal triglyceride transfer protein (MTP) regulates intracellular lipolysis by inhibiting adipose triglyceride lipase activity. The aim of this study was to investigate the impact of adipose MTP deficiency on MASLD. METHODS/UNASSIGNED: RESULTS/UNASSIGNED: CONCLUSION/UNASSIGNED:These findings highlight the importance of regulated FA flux from adipose tissue to the liver and the liver's adaptive capacity to utilize adipose-derived FAs in maintaining hepatic health. Modulation of adipocyte FA release may represent a therapeutic strategy to reduce hepatic steatosis. IMPACT AND IMPLICATIONS/UNASSIGNED:This study provides significant insights into the role of adipose-specific microsomal triglyceride transfer protein in regulating hepatic lipid metabolism and its potential implications for treating metabolic dysfunction-associated steatotic liver disease. By demonstrating that microsomal triglyceride transfer protein deficiency in adipose tissue leads to increased fatty acid oxidation and reduced hepatic steatosis through enhanced PPARα activation, the research underscores the importance of adipose-liver crosstalk in maintaining liver health. These findings suggest that targeting adipocyte fatty acid release could be a promising therapeutic strategy to mitigate hepatic lipid accumulation and combat metabolic dysfunction-associated steatotic liver disease, offering a novel approach to addressing this growing health issue.
PMCID:12657731
PMID: 41321937
ISSN: 2589-5559
CID: 5974542

Post-hurricane fluid conservation measures fail to reduce IV fluid use in critically ill children

Dixon, Celeste G; Odum, James D; Kothari, Ulka; Martin, Susan D; Fitzgerald, Julie C; Shah, Ami; Dapul, Heda; Braun, Chloe G; Barbera, Andrew; Terry, Nina; Weiss, Scott L; Hasson, Denise C; Dziorny, Adam C
BACKGROUND:There are risks associated with excessive intravenous fluid (IVF) administration in critically ill children. Previous efforts have described opportunities to reduce positive cumulative fluid balance (CFB) in this population but have not been widely implemented. In the wake of Hurricane Helene, a national IVF shortage led to the implementation of IVF conservation guidelines. We sought to determine if this was associated with a reduction in IVF use and CFB. METHODS:The present study is a four-site cohort study of critically ill children utilizing a federated data collection framework to extract patient age, sex, weight, and daily fluid intake/output for days 1-4 of all admissions 28 days prior to and 28 days after the implementation of IVF conservation guidelines. Guidelines were individualized per institution. Total fluid intake, total IVF intake, % intake from IVF, and % CFB were compared between pre- and post-IVF conservation groups. RESULTS:All sites had similar conservation recommendations. There were 633 patients admitted pre- and 619 patients admitted post-IVF conservation guideline implementation, with similar age and weight distributions. There was no significant difference in IVF use pre- and post-IVF conservation; 29-35% of patients had > 5% CFB on day 1 pre-IVF conservation while 27-39% did post-conservation, with increasing numbers on day 2. CONCLUSIONS:Even in the setting of a national IVF shortage, simple recommendations without structured change were insufficient to change IVF administration practices. This indicates additional practices will be needed to reduce IVF intake and % CFB in this vulnerable population.
PMID: 40828175
ISSN: 1432-198x
CID: 5908922

Application of Generative AI to enhance obstetrics and gynecology research

Kawakita, Tetsuya; Wong, Meilssa S; Gibson, Kelly S; Gupta, Megha; Gimovsky, Alexis; Moussa, Hind N; Heo, Hye
The rapid evolution of large-language models such as ChatGPT, Claude, and Gemini is reshaping the methodological landscape of obstetrics and gynecology (OBGYN) research. This narrative review provides a comprehensive account of generative AI capabilities, key use-cases, and recommended safeguards for investigators. First, generative AI expedites hypothesis generation, enabling researchers to interrogate vast corpora and surface plausible, overlooked questions. Second, it streamlines systematic reviews by composing optimized search strings, screening titles and abstracts, and identifying full-text discrepancies. Third, AI assistants can draft reproducible analytic code, perform preliminary descriptive or inferential analyses, and create publication-ready tables and figures. Fourth, the models support scholarly writing by suggesting journal-specific headings, refining prose, harmonizing references, and translating technical content for multidisciplinary audiences. Fifth, they augment peer-review and editorial workflows by delivering evidence-focused critiques. In educational settings, these models can create adaptive curricula and interactive simulations for trainees, fostering digital literacy and evidence-based practice early in professional development among clinicians. Integration into clinical decision-support pipelines is also foreseeable, warranting proactive governance. Notwithstanding these opportunities, responsible use demands vigilant oversight. Large-language models occasionally fabricate citations or misinterpret domain-specific data ("hallucinations"), potentially propagating misinformation. Outputs are highly prompt-dependent, creating a reliance on informed prompt engineering that may disadvantage less technical clinicians. Moreover, uploading protected health information or copyrighted text raises privacy, security, and intellectual-property concerns. We outline best-practice recommendations: maintain human verification of all AI-generated content; cross-validate references with primary databases; employ privacy-preserving, on-premises deployments for sensitive data; document prompts for reproducibility; and disclose AI involvement transparently. In summary, generative AI offers a powerful adjunct for OBGYN scientists by accelerating topic formulation, evidence synthesis, data analysis, manuscript preparation, and peer review. When coupled with rigorous oversight and ethical safeguards, these tools can enhance productivity without compromising scientific integrity. Future studies should quantify accuracy, bias, and downstream patient impact.
PMID: 40393680
ISSN: 1098-8785
CID: 5853042

Role of hypertension in the cardiovascular-kidney-metabolic syndrome among black adults: The Jackson Heart Study

Ghazi, Lama; Dubal, Medha; Bertoni, Alain; Carson, April; Young, Bessie A; Lewis, Cora E; Alanaeme, Chibuike J; Johnson, Dayna A; Shimbo, Daichi; Foti, Kathryn; Colantonio, Lisandro D; Arabadjian, Milla; Tanner, Rikki; Muntner, Paul
The cardiovascular-kidney-metabolic (CKM) syndrome consists of four progressive stages and is characterized by the interaction of metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). We assessed the prevalence of hypertension in CKM and its role in progression to more advanced stages. We included 2118 Black adults from the Jackson Heart Study without a history of coronary heart disease, heart failure, stroke or stage 0 CKM (normal weight, no metabolic risk factors or CVD) at baseline. Participants were categorized into CKD stage: Stage 1: overweight/obesity, abdominal obesity or dysfunctional adipose tissue without metabolic risk factors or subclinical CVD; Stage 2: metabolic risk factors (hypertension, diabetes, hypertriglyceridemia, metabolic syndrome or CKD); or Stage 3: subclinical CVD. We used Cox proportional hazards regression to estimate the hazard ratio (HR) of developing stage 4 CKM, defined by a CVD event, in participants with hypertension and stages 2 and 3 CKM. At baseline, 20.2, 69.1 and 10.6% of participants had stage 1, 2 and 3 CKM, respectively. Hypertension was the most common metabolic risk factor in participants with stage 2 and 3 CKM with a prevalence of 80 and 95%, respectively. Incidence rates (95%CI) of stage 4 CKM per 1000 person-years were 1.4 (0.4, 2.4) for stage 1 CKM, 7.5 (6.1, 8.9) for stage 2 CKM with hypertension, and 26.6 (19.8, 33.3) for stage 3 CKM with hypertension. The HRs (95% CI) for developing stage 4 CKM were 3.25 (1.56, 6.80) and 5.11 (2.05,12.78) among participants with hypertension and stage 2 and 3 CKM versus stage 1 CKM, respectively. Hypertension was associated with an increased risk for progression to stage 4 CKM among Black adults.
PMCID:12685740
PMID: 41046247
ISSN: 1476-5527
CID: 5976992

Extracellular Vesicles From Chylomicron-Treated Endothelial Cells Drive Macrophage Inflammation

Tilp, Anna; Nasias, Dimitris; Carley, Andrew L; Park, Min Young; Mooring, Ashley; Tirumalasetty, Munichandra Babu; Abumrad, Nada A; Wang, Yang; Miao, Qing Robert; Lewandowski, E Douglas; Alemán, José O; Goldberg, Ira J; Cabodevilla, Ainara G
BACKGROUND/UNASSIGNED:Movement of circulating lipids into tissues and arteries requires transfer across the endothelial cell (EC) barrier. This process allows the heart to obtain fatty acids, its chief source of energy, and apoB-containing lipoproteins to cross the arterial endothelial barrier, leading to cholesterol accumulation in the subendothelial space. Multiple studies have established elevated postprandial TRLs (triglyceride-rich lipoproteins) as an independent risk factor for cardiovascular disease. We explored how chylomicrons affect ECs and transfer their fatty acids across the EC barrier. METHODS/UNASSIGNED:C]oleate, we studied the uptake and release of this labeled by ECs. RESULTS/UNASSIGNED:]C labeled chylomicron triglycerides exited ECs primarily in phospholipids. EVs from chylomicron-treated versus untreated ECs were larger, more abundant, and contained specific microRNAs. Treatment of macrophages and naive ECs with media from chylomicron-treated ECs increased expression of inflammatory genes. CONCLUSIONS/UNASSIGNED:EC chylomicron metabolism produces EVs that increase macrophage inflammation and create LDs. Media containing these EVs also increases EC inflammation, illustrating an autocrine inflammatory process. Fatty acids within chylomicron triglycerides are converted to phospholipids within EVs. Thus, EC uptake of chylomicrons constitutes an important pathway for vascular inflammation and tissue lipid acquisition.
PMID: 41099102
ISSN: 1524-4636
CID: 5955042

Global disparities in adrenaline access: A World Allergy Organization call for equity in anaphylaxis care [Editorial]

Morais-Almeida, Mário; Martin, Bryan L; Turner, Paul J; Fiocchi, Alessandro; Ebisawa, Motohiro; Wing-Kin Wong, Gary; Ansotegui, Ignacio J; Al-Nesf Al-Mansouri, Maryam Ali; Bernstein, Jonathan A; Chantaphakul, Hiroshi; Chikovani, Tinatin; Fasano, Mary Beth; Fonacier, Luz; Giavina-Bianchi, Pedro; Gómez, René Maximiliano; González-Díaz, Sandra N; Hossny, Elham; Lang, David M; Morita, Hideaki; Ortegal Martell, José Antonio; Papadopoulos, Nikolaos G; Tanno, Luciana Kase
PMCID:12702309
PMID: 41399690
ISSN: 1939-4551
CID: 5979182

EEG-related deep tissue injuries in critically ill pediatric patients: A single institution quality improvement project

Willard, Joel; Creed, Megan; Philip, Lincy; Varughese, Robin; Kothare, Sanjeev
INTRODUCTION/BACKGROUND:Neurologic complications, including seizures, are common in pediatric patients undergoing heart surgery, especially those requiring postoperative extracorporeal membrane oxygenation (ECMO), requiring prompt, vigilant postoperative monitoring. Prolonged EEG monitoring in critically ill children presents a risk of scalp/pressure injuries. The skin's sensitivity to microcirculatory changes can also provide valuable insights into the patient's overall tissue perfusion, making it a critical component in the management of these vulnerable patients. METHODS:We initiated a quality improvement (QI) project to assess and reduce scalp injuries related to prolonged EEG monitoring in critically ill neonates and infants. The project involved reviewing baseline data, which included 2336 inpatient video EEGs performed from January 2022 to December 2024, and implementing interventions to improve skin safety during electrode placement, while incorporating best practices from ACNS and ASET guidelines. RESULTS:Five critically ill infants developed deep tissue injuries (DTIs) related to EEG electrodes, with most injuries occurring over the occipital region. The frequency of scalp injuries decreased from 0.30% in 2022 to 0% in 2024 after implementing the QI protocol, and was observed in conditions with known hypoperfusion. DISCUSSION/CONCLUSIONS:Electrode-related skin injuries are a common complication of prolonged EEG monitoring, particularly in critically ill pediatric patients. Our findings suggest that adherence to expert guidelines and tailored skin care protocols focused on skin preparation, electrode application, and monitoring parameters can reduce the risk of electrode-related skin injuries. Further research is needed to refine safety protocols and address the unique skin care challenges faced by this high-risk population.
PMID: 40910437
ISSN: 1950-6945
CID: 5950122

Meta-Analysis of AI Integration in Abdominal Imaging for Liver Fibrosis and MASLD: Evaluating Diagnostic Accuracy and Clinical Impact

Pugliesi, Rosa Alba; Ben Mansour, Karim; Apitzsch, Jonas; Papachristodoulou, Angeliki; Rafailidis, Vasileios; Katz, Douglas S
PMCID:12693291
PMID: 41375769
ISSN: 2077-0383
CID: 5977612

Protocol for the process evaluation of a randomised clinical trial of incremental-start versus conventional haemodialysis: the TwoPlus study

Murea, Mariana; Foley, Kristie L; Gautam, Samir C; Flythe, Jennifer E; Raimann, Jochen G; Abdel-Rahman, Emaad; Awad, Alaa S; Niyyar, Vandana Dua; Kovach, Cassandra; Roberts, Glenda V; Jefferson, Nicole M; Conway, Paul T; Rosales, Laura M; Woldemichael, Jobira; Sheikh, Hiba I; Raman, Gaurav; Huml, Anne M; Knicely, Daphne H; Hasan, Irtiza; Makadia, Bhaktidevi; Lea, Janice; Daugirdas, John T; Gencerliler, Nihan; Divers, Jasmin; Kotanko, Peter; ,; Nwaozuru, Ucheoma C
INTRODUCTION/BACKGROUND:Process evaluation provides insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines the protocol for a process evaluation embedded in a hybrid type 1 effectiveness-implementation randomised clinical trial of incremental-start haemodialysis (HD) versus conventional HD delivered to patients starting chronic dialysis (the TwoPlus Study). The trial will simultaneously assess the effectiveness of incremental-start HD in real-world settings and the implementation strategies needed to successfully integrate this intervention into routine practice. This manuscript describes the rationale and methods used to capture how incremental-start HD is implemented across settings and the factors influencing its implementation success or failure within this trial. METHODS AND ANALYSIS/METHODS:We will use the Consolidated Framework for Implementation Research (CFIR) and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) frameworks to inform process evaluation. Mixed methods include surveys conducted with treating providers (physicians) and dialysis personnel (nurses and dialysis administrators); semi-structured interviews with patient participants, caregivers of patient participants, treating providers (physicians and advanced practice practitioners), dialysis personnel (nurses, dieticians and social workers); and focus group meetings with study investigators and stakeholder partners. Data will be collected on the following implementation determinants: (a) organisational readiness to change, intervention acceptability and appropriateness; (b) inner setting characteristics underlying barriers and facilitators to the adoption of HD intervention at the enrollment centres; (c) external factors that mediate implementation; (d) adoption; (e) reach; (f) fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and (g) sustainability, to assess barriers and facilitators to maintaining intervention. Qualitative and quantitative data will be analysed iteratively and triangulated following a convergent parallel and pragmatic approach. Mixed methods analysis will use qualitative data to lend insight to quantitative findings. Process evaluation is important to understand factors influencing trial outcomes and identify potential contextual barriers and facilitators for the potential implementation of incremental-start HD into usual workflows in varied outpatient dialysis clinics and clinical practices. The process evaluation will help interpret and contextualise the trial clinical outcomes' findings. ETHICS AND DISSEMINATION/BACKGROUND:The study protocol was approved by the Wake Forest University School of Medicine Institutional Review Board (IRB). Findings from this study will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT05828823.
PMID: 41314824
ISSN: 2044-6055
CID: 5968882

From NICU to home: meeting the mental health needs of families after discharge

Swenson, Sarah A; Desai, Riddhi K; Velagala, Suganthinie; Hoge, Margaret K; Htun, Zeyar; Carr, Cara Beth; Roush, Kelly; Liu, Cindy H; Maddox, Katherine; Erdei, Carmina
Families of infants hospitalized in the neonatal intensive care unit (NICU) are at an increased risk for depression, anxiety, and trauma symptoms that often persist well beyond transition from the NICU. While NICU professionals provide vital medical care for high-risk infants, they also offer interdisciplinary support for families, including collaboration with psychosocial and psychiatric services in select settings. Despite psychosocial support systems often being present during NICU hospitalization, significant gaps remain in post-NICU mental health support for parents. Comprehensive discharge preparation and outpatient follow-up planning for infants, as well as their families, are essential to optimize both long-term outcomes and the well-being of the entire family unit. In this paper, we review current evidence regarding mental health risks for families during transitions of care and highlight practice recommendations and advocacy opportunities for enhanced family-centered, interdisciplinary follow-up care after transition from the NICU.
PMID: 41299095
ISSN: 1476-5543
CID: 5968542