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1.
Cureus ; 16(3): e55304, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38559518

RESUMO

INTRODUCTION: AI chatbots are being increasingly used in healthcare settings. There is growing interest in using AI to assist in patient education. Currently, extensive healthcare information is found online but is often too complex to understand. Our objective is to determine if physicians can recommend the free version of ChatGPT version 3.5 (OpenAI, San Francisco, CA, USA) for patients to simplify text from the American Academy of Ophthalmology (AAO) in English and Spanish. This version of ChatGPT was assessed in this study due to its increased accessibility across various patient populations. METHODS: Fifteen articles were chosen from AAO in both languages and simplified with ChatGPT 10 times each. The readability of original and simplified articles was assessed with the Flesch Reading Ease and Gunning Fog Index for English and Fernández Huerta, Gutiérrez, Szigriszt-Pazo, INFLESZ, and Legibilidad-µ for Spanish. Grade levels to assess readability were calculated with Flesch Kincaid Grade Level and Crawford Nivel-de-Grado. Mean, standard deviation, and two-tailed t-tests were performed to assess differences before and after simplification. RESULTS: Average grade levels before and after simplification were as follows: English 8.43±1.17 to 8.9±2.1 (p=0.41) and Spanish 5.3±0.34 to 4.1±1.1 (p=0.0001). Spanish articles were significantly simplified per Legibilidad-µ (p=0.003). No significant difference was noted for other scales. CONCLUSIONS: The readability of AAO articles in English worsened without significance but significantly improved in Spanish. This may result from simpler syllable structures and a lesser overall vocabulary in Spanish. With increased testing, physicians can recommend ChatGPT for Spanish-speaking patients to improve health literacy.

2.
Cureus ; 16(3): e56596, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646359

RESUMO

Acne vulgaris is a prevalent chronic inflammatory skin condition with significant implications for quality of life, particularly among adolescents and young adults. Recent advancements in understanding its pathophysiology and developing novel therapeutic modalities have reshaped the landscape of acne management. This review provides an overview of recent trends in acne management, focusing on clinical studies conducted in the past decade. Key findings include insights into acne pathogenesis, emerging treatment modalities, comparative effectiveness of traditional and emerging therapies, and considerations for patient-centered care. The review underscores the importance of staying updated with recent clinical studies to provide evidence-based care and optimize patient treatment outcomes. Moreover, it highlights the need for continued research efforts to develop personalized treatment approaches, explore combination therapies, and address the psychosocial impact of acne. Collaborative endeavors between clinicians and researchers are essential to advance the field of acne management and improve patient outcomes.

3.
Nucl Med Commun ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38632971

RESUMO

OBJECTIVE: Hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) have limited therapeutic options, Re-188 lipiodol transarterial therapy being one of them. We aimed to assess the safety and efficacy of Re-188 lipiodol exclusively in HCC with PVT as well as to compare two chelating agents for the synthesis of Re-188 lipiodol: novel bis-(diethyldithiocarbamato) nitrido (N-DEDC) with existing acetylated 4-hexadecyl 1-2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol [(A)HDD]. METHODS: Patients with radiological diagnosis of HCC with PVT having Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and Child Pugh score (PS) A or B were recruited. Patients received an empirical dose of transarterial Re-188 lipiodol, labelled with (A)HDD or N-DEDC. Radiological response on MRI (modified response evaluation criteria in solid tumors), biochemical response with serum alpha fetoprotein and clinical response with ECOG PS was assessed at three months and survival was estimated at the end of the study. RESULTS: Fifteen therapies were performed in 14 patients with a median age of 62 years (range: 41-70 years). Eight therapies were with Re-188 (A)HDD lipiodol and seven with Re-188 N-DEDC lipiodol. Overall mean injected dose was 2.6 ±â€…0.37 GBq. Radiological objective response rate was 31% and disease control rate was 85%. Mean overall survival was 14.21 months and mean progression free survival was 10.23 months. Percentage survival assessed at 3, 6 and 9 months was 93%, 64% and 57%, respectively. Safety parameters, response and survival outcome were comparable for (A)HDD and N-DEDC groups. CONCLUSION: Transarterial Re-188 lipiodol in HCC with PVT is safe and effective in disease control as well as improving survival outcome. Additionally, cost-effective and high-yielding novel agent N-DEDC appears to be a comparable alternative to (A)HDD for the same.

5.
Cureus ; 16(1): e52960, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38406023

RESUMO

Lupus erythematosus is an autoimmune disorder with varied clinical features. Discoid Lupus Erythematosus (DLE) presents as erythematous, raised plaques. The patients might present with photosensitivity, arthralgia, and nail changes. However, dermoscopy, clinical features, and laboratory markers like high titers of Antinuclear antibodies (ANA) help in clenching the diagnosis. We report a patient in her mid-60s presented with non-healing ulcers oozing pus discharge associated with pain and joint stiffness. Thus, a series of investigations, treatment modifications, and the healing progression of the lesions highlight the importance of retrospective diagnosis.

6.
Plant Sci ; 342: 112024, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38325661

RESUMO

Plant growth relies on the mineral nutrients present in the rhizosphere. The distribution of nutrients in soils varies depending on their mobility and capacity to bind with soil particles. Consequently, plants often encounter either low or high levels of nutrients in the rhizosphere. Plant roots are the essential organs that sense changes in soil mineral content, leading to the activation of signaling pathways associated with the adjustment of plant architecture and metabolic responses. During differential availability of minerals in the rhizosphere, plants trigger adaptation strategies such as cellular remobilization of minerals, secretion of organic molecules, and the attenuation or enhancement of root growth to balance nutrient uptake. The interdependency, availability, and uptake of minerals, such as phosphorus (P), iron (Fe), zinc (Zn), potassium (K), nitrogen (N) forms, nitrate (NO3-), and ammonium (NH4+), modulate the root architecture and metabolic functioning of plants. Here, we summarized the interactions of major nutrients (N, P, K, Fe, Zn) in shaping root architecture, physiological responses, genetic components involved, and address the current challenges associated with nutrient-nutrient interactions. Furthermore, we discuss the major gaps and opportunities in the field for developing plants with improved nutrient uptake and use efficiency for sustainable agriculture.


Assuntos
Plantas , Solo , Plantas/metabolismo , Agricultura , Minerais/metabolismo , Nutrientes , Raízes de Plantas/metabolismo
7.
Bone Joint J ; 106-B(1): 28-37, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38160689

RESUMO

Aims: This study aims to determine the rate of and risk factors for total knee arthroplasty (TKA) after operative management of tibial plateau fractures (TPFs) in older adults. Methods: This is a retrospective cohort study of 182 displaced TPFs in 180 patients aged ≥ 60 years, over a 12-year period with a minimum follow-up of one year. The mean age was 70.7 years (SD 7.7; 60 to 89), and 139/180 patients (77.2%) were female. Radiological assessment consisted of fracture classification; pre-existing knee osteoarthritis (OA); reduction quality; loss of reduction; and post-traumatic OA. Fracture depression was measured on CT, and the volume of defect estimated as half an oblate spheroid. Operative management, complications, reoperations, and mortality were recorded. Results: Nearly half of the fractures were Schatzker II AO B3.1 fractures (n = 85; 47%). Radiological knee OA was present at fracture in 59/182 TPFs (32.6%). Primary management was fixation in 174 (95.6%) and acute TKA in eight (4.4%). A total of 13 patients underwent late TKA (7.5%), most often within two years. By five years, 21/182 12% (95% confidence interval (CI) 6.0 to 16.7) had required TKA. Larger volume defects of greater depth on CT (median 15.9 mm vs 9.4 mm; p < 0.001) were significantly associated with TKA requirement. CT-measured joint depression of > 12.8 mm was associated with TKA requirement (area under the curve (AUC) 0.766; p = 0.001). Severe joint depression of > 15.5 mm (hazard ratio (HR) 6.15 (95% CI 2.60 to 14.55); p < 0.001) and pre-existing knee OA (HR 2.70 (95% CI 1.14 to 6.37); p = 0.024) were independently associated with TKA requirement. Where patients with severe joint depression of > 15.5 mm were managed with fixation, 11/25 ultimately required TKA. Conclusion: Overall, 12% of patients aged ≥ 60 years underwent TKA within five years of TPF. Severe joint depression and pre-existing knee arthritis were independent risk factors for both post-traumatic OA and TKA. These features should be investigated as potential indications for acute TKA in older adults with TPFs.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Fraturas da Tíbia , Fraturas do Planalto Tibial , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Artroplastia do Joelho/efeitos adversos , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Estudos Retrospectivos , Fraturas da Tíbia/complicações , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Articulação do Joelho/cirurgia
8.
Cureus ; 15(9): e45911, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37885556

RESUMO

PURPOSE AND DESIGN: To evaluate the accuracy and bias of ophthalmologist recommendations made by three AI chatbots, namely ChatGPT 3.5 (OpenAI, San Francisco, CA, USA), Bing Chat (Microsoft Corp., Redmond, WA, USA), and Google Bard (Alphabet Inc., Mountain View, CA, USA). This study analyzed chatbot recommendations for the 20 most populous U.S. cities. METHODS: Each chatbot returned 80 total recommendations when given the prompt "Find me four good ophthalmologists in (city)." Characteristics of the physicians, including specialty, location, gender, practice type, and fellowship, were collected. A one-proportion z-test was performed to compare the proportion of female ophthalmologists recommended by each chatbot to the national average (27.2% per the Association of American Medical Colleges (AAMC)). Pearson's chi-squared test was performed to determine differences between the three chatbots in male versus female recommendations and recommendation accuracy. RESULTS: Female ophthalmologists recommended by Bing Chat (1.61%) and Bard (8.0%) were significantly less than the national proportion of 27.2% practicing female ophthalmologists (p<0.001, p<0.01, respectively). ChatGPT recommended fewer female (29.5%) than male ophthalmologists (p<0.722). ChatGPT (73.8%), Bing Chat (67.5%), and Bard (62.5%) gave high rates of inaccurate recommendations. Compared to the national average of academic ophthalmologists (17%), the proportion of recommended ophthalmologists in academic medicine or in combined academic and private practice was significantly greater for all three chatbots. CONCLUSION: This study revealed substantial bias and inaccuracy in the AI chatbots' recommendations. They struggled to recommend ophthalmologists reliably and accurately, with most recommendations being physicians in specialties other than ophthalmology or not in or near the desired city. Bing Chat and Google Bard showed a significant tendency against recommending female ophthalmologists, and all chatbots favored recommending ophthalmologists in academic medicine.

9.
Nucl Med Mol Imaging ; 57(5): 235-242, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37720877

RESUMO

Purpose: Hereditary tumor syndrome Von Hippel-Lindau (VHL) disease is characterized by various benign and malignant tumors that are known to express somatostatin receptors (SSTR). We evaluated the role of 68Ga-DOTANOC PET/CT scan in patients with positive germline mutation of the VHL gene, presented initially or on follow-up, for the detection of recurrent or synchronous/metachronous lesions. Methods: Fourteen patients (8 males; 6 females) with mean age 30 ± 9.86 years were retrospectively analyzed, were tested positive for VHL on gene dosage analysis, and underwent 68 Ga-DOTANOC PET/CT scan for disease evaluation. The number and site of lesions were determined. The tracer uptake was analyzed semi-quantitatively by calculating the maximum standardized uptake values (SUVmax) of lesion. Results: Four of the 14 patients underwent scan for initial diagnosis as baseline, 6 patients for post-therapy disease status, and 4 patients for initial diagnosis as well as follow-up evaluation of the disease. A total of 67 lesions were detected in 14 patients. The sites of lesions were cerebellar/vertebral/spinal (17; mean SUVmax = 7.85); pancreatic neuroendocrine tumor (NET) (11; mean SUVmax = 20.64); retina (3; mean SUVmax = 10.46); pheochromocytoma (10; mean SUVmax = 16.32); paragangliomas (3; mean SUVmax = 10.65); pancreatic cyst (9; mean SUVmax = 2.54); and renal cyst (8; mean SUVmax = 1.56) and miscellaneous lesions constituted 6 lesions. Conclusion: Our results show that 68 Ga-DOTANOC PET/CT may be a useful modality for screening and follow-up of associated tumors in patients with germline gene mutation for VHL. It can be used as a one-stop imaging modality for VHL patients and may substitute for separate radiological investigations, making it more convenient for patients in terms of time and cost.

10.
Ann Surg Oncol ; 30(13): 8610-8620, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37624518

RESUMO

INTRODUCTION: The association of time to treatment (TTT) with survival remains unclear in pancreatic adenocarcinoma (PDAC). In this study, we evaluate the recent trends in TTT, causes for delay, and its effect on survival. METHODS: We included patients with PDAC of all stages from the National Cancer Database (2004-2020) who underwent either surgery or chemotherapy/radiotherapy (CT/RT). TTT was defined as the duration between tissue diagnosis and first treatment. Linear regression (ß) was used to study the temporal trends in time delay. RESULTS: A total of 239,638 patients were included. The median TTT was 25 days. Using multivariable analysis, we found that increasing age (OR 1.48), female gender (OR 1.04), Black race (OR 1.3), lower educational status (OR 1.2), Medicaid, Medicare insurance, and uninsured (OR 1.2, 1.5, and 1.2, respectively), treatment at academic centers (OR 1.3), higher Charlson-Deyo comorbidity index (OR 1.2), and CT/RT (OR 1.5) were associated with increased TTT. There was a steady rise in median TTT from 21 to 28 days between 2004 and 2020 (ß = 0.3), suggestive of a worsening trend. Concurrently, there was an increasing trend in utilization of neoadjuvant CT/RT between 2004 and 2020 in early-stage PDAC. On Cox regression, TTT delay was associated with poor overall survival in stage I-IV patients (HR 1.1, 1.1, 1.09, and 1.53, respectively). CONCLUSIONS: Delayed treatment approaching 2 months was observed in 10% of the population. The rising temporal trend in TTT may be attributed to the increasing shift toward neoadjuvant CT/RT in early-stage PDAC and/or the increasing use of tissue biopsy prior to surgery.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Feminino , Idoso , Estados Unidos , Prognóstico , Neoplasias Pancreáticas/patologia , Adenocarcinoma/patologia , Tempo para o Tratamento , Medicare , Estudos Retrospectivos , Neoplasias Pancreáticas
11.
Sci Rep ; 13(1): 13267, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582799

RESUMO

We develop a method to estimate the quality of processing routes in a wafer fabrication process. Ranking such routes can be useful for identifying the "best" and "worst" routes when making adjustments to recipes. Route categorization is also useful in developing efficient scheduling algorithms. In particular, we propose a method for ranking routes based on count-based metrics such as the number of defects on a wafer. We start with a statistical model to produce a "local" ranking of a tool and then build a "global" ranking via a heuristic procedure. Creating a fully statistical procedure for ranking routes in semiconductor fabrication plants is virtually impossible, given the number of possible routes and the limited data available. Nonetheless, our discussions with working engineers indicate that even approximate rankings are useful for making better operational decisions.

12.
Int J Biol Macromol ; 250: 126230, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37558033

RESUMO

This study utilizes different emerging green extraction technologies to recover maximum value-added products from Kappaphycus alvarezii and evaluate their bio-functional properties. Using the supercritical fluid extraction (SFE) method, the total lipid yield of 0.21 ± 0.2 % was obtained from the biomass. Linoleic acid, eicosapentaenoic acid, arachidonic acid, γ-linolenic acid, and docosahexaenoic acid were present in higher concentrations (9.12 %) in the lipid extracted with SFE as compared to hexane (5.5 %). Using an ultrasonication assisted approach, ~56 % of κ-carrageenan was recovered from SFE residual biomass, which contains 28.5 ± 1.9 % sulfate content. It exhibited a monosaccharide content of 3,6-anhydrogalactose (~24 %) and galactose (~53 %), as well as rheological properties within FAO limitations that can be explored for food-grade applications. ~58 % of the total protein (12.5 %) from SFE residual biomass was recovered using subcritical water hydrolysis method. The effectiveness of κ-carrageenan in suppressing the 3CLpro of SARS-CoV-2 using in vitro and in silico approaches was investigated. κ-Carrageenan effectively inhibited the main protease by up to 93 % at 1.6 mg mL-1. In silico results revealed that κ-carrageenan successfully binds to the active site of the main protease while retaining the structural integrity and stability of protein-ligand complexes.

13.
Int J Biol Macromol ; 248: 125950, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37487999

RESUMO

The current study investigated the role of fucoidan from Padina tetrastromatica and Turbinaria conoides against 3-chymotrypsin like protease (3CLpro) and receptor binding domain (RBD) spike protein of SARS-CoV-2 using an invitro and computational approach. The 3CLpro and RBD genes were successfully cloned in pET28a vector, expressed in BL-21DE3 E. coli rosetta cells and purified by ion exchange affinity and size exclusion chromatography. Fucoidan extracted from both biomass using green approach, subcritical water, was found to inhibit 3CLpro of SARS-CoV-2 with an IC50 value of up to 0.35 mg mL-1. However, fucoidan was found to be inactive against the RBD protein. Molecular docking studies demonstrated that fucoidan binds to the active sites of 3CLpro with an affinity of -5.0 kcal mol-1. In addition, molecular dynamic simulations recorded stabilized interactions of protein-ligand complexes in terms of root mean square deviation, root mean square fluctuation, the radius of gyration, solvent accessible surface area and hydrogen bond interaction. The binding energy of fucoidan with 3CLpro was determined to be -101.821 ± 12.966 kJ mol-1 using Molecular Mechanic/Poisson-Bolt-Boltzmann Surface Area analysis. Fucoidan satisfies the Absorption, Distribution, Metabolism, and Excretion (ADME) properties, including Lipinski's rule of five, which play an essential role in drug design. According to the toxicity parameters, fucoidan does not exhibit skin sensitivity, hepatotoxicity, or AMES toxicity. Therefore, this work reveals that fucoidan from brown macroalgae could act as possible inhibitors in regulating the function of the 3CLpro protein, hence inhibiting viral replication and being effective against COVID-19.


Assuntos
COVID-19 , Alga Marinha , Humanos , SARS-CoV-2 , Escherichia coli , Simulação de Acoplamento Molecular , Quimases , Inibidores de Proteases/farmacologia , Simulação de Dinâmica Molecular , Antivirais/farmacologia
14.
West J Emerg Med ; 24(3): 622-628, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37278794

RESUMO

INTRODUCTION: Point-of-care ultrasound (POCUS) plays a pivotal role in evaluating ocular complaints in the emergency department (ED). The rapid and non-invasive nature of ocular POCUS makes it a safe and informative imaging modality. Previous studies have investigated using ocular POCUS to diagnose posterior vitreous detachment (PVD), vitreous hemorrhage (VH), and retinal detachment (RD); however, there are few studies that assess image optimization techniques and how they impact the overall accuracy of ocular POCUS. METHODS: We performed a retrospective review of ED patients who received ocular POCUS examinations and ophthalmology consultations as part of their evaluation for eye complaints at our urban, Level I trauma center ED from November 2017-January 2021. Of 706 exams, 383 qualified for the study. In this study we primarily investigated how stratified gain levels impact the accuracy of ocular POCUS for detection of any posterior chamber pathology and, secondarily, whether stratified gain levels impact the accuracy of detecting RD, VH, and PVD specifically. RESULTS: The images were found to have an overall sensitivity of 81% (76-86%), specificity of 82% (76-88%), positive predictive value (PPV) of 86% (81-91%), and negative predictive value (NPV) of 77% (70-83%). Images acquired with a gain of (25, 50] had a sensitivity of 71% (61-80%), specificity of 95% (85-99%), PPV of 96% (88-99%), and NPV of 68% (56-78%). Images acquired with a gain of (50, 75] had a sensitivity of 85% (73-93%), specificity of 85% (72-93%), PPV of 86% (75-94%), and NPV of 83% (70-92%). Images acquired with a high gain (75, 100] had a sensitivity of 91% (82-97%), specificity of 67% (53-79%), PPV of 78% (68-86%), and NPV of 86% (72-95%). CONCLUSION: In the ED setting, high (75, 100] gain on ocular POCUS scanning has a higher degree of sensitivity for detecting any posterior chamber abnormality, as compared to low (25, 50] gain levels. Thus, incorporating the use of high gain for ocular POCUS exams produces a more effective tool for ocular pathologies in acute care settings and may be particularly valuable in resource-limited settings.


Assuntos
Descolamento Retiniano , Descolamento do Vítreo , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Ultrassonografia/métodos , Olho/diagnóstico por imagem , Descolamento Retiniano/diagnóstico por imagem , Serviço Hospitalar de Emergência
15.
Int J Mol Sci ; 24(9)2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37175604

RESUMO

Accumulating evidence highlights protein O-GlcNAcylation as a putative pathogenic contributor of diabetic vascular complications. We previously reported that elevated protein O-GlcNAcylation correlates with increased atherosclerotic lesion formation and VSMC proliferation in response to hyperglycemia. However, the role of O-GlcNAc transferase (OGT), regulator of O-GlcNAc signaling, in the evolution of diabetic atherosclerosis remains elusive. The goal of this study was to determine whether smooth muscle OGT (smOGT) plays a direct role in hyperglycemia-induced atherosclerotic lesion formation and SMC de-differentiation. Using tamoxifen-inducible Myh11-CreERT2 and Ogtfl/fl mice, we generated smOGTWT and smOGTKO mice, with and without ApoE-null backgrounds. Following STZ-induced hyperglycemia, smOGTWT and smOGTKO mice were kept on a standard laboratory diet for the study duration. In a parallel study, smOGTWTApoE-/- and smOGTKOApoE-/- were initiated on Western diet at 8-wks-age. Animals harvested at 14-16-wks-age were used for plasma and tissue collection. Loss of smOGT augmented SM contractile marker expression in aortic vessels of STZ-induced hyperglycemic smOGTKO mice. Consistently, smOGT deletion attenuated atherosclerotic lesion lipid burden (Oil red O), plaque area (H&E), leukocyte (CD45) and smooth muscle cell (ACTA2) abundance in Western diet-fed hyperglycemic smOGTKOApoE-/- mice. This was accompanied by increased SM contractile markers and reduced inflammatory and proliferative marker expression. Further, smOGT deletion attenuated YY1 and SRF expression (transcriptional regulators of SM contractile genes) in hyperglycemic smOGTKOApoE-/- and smOGTKO mice. These data uncover an athero-protective outcome of smOGT loss-of-function and suggest a direct regulatory role of OGT-mediated O-GlcNAcylation in VSMC de-differentiation in hyperglycemia.


Assuntos
Aterosclerose , Hiperglicemia , Camundongos , Animais , Dieta Ocidental/efeitos adversos , Camundongos Knockout , Aterosclerose/genética , Aterosclerose/metabolismo , Miócitos de Músculo Liso/metabolismo , Hiperglicemia/metabolismo , Músculo Liso Vascular/metabolismo , Apolipoproteínas E/genética , Camundongos Endogâmicos C57BL
16.
J Neurosci Res ; 101(8): 1324-1344, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37031439

RESUMO

Metabolic syndrome (MetS), characterized by hyperglycemia, obesity, and hyperlipidemia, can increase the risk of developing late-onset dementia. Recent studies in patients and mouse models suggest a putative link between hyperphosphorylated tau, a component of Alzheimer's disease-related dementia (ADRD) pathology, and cerebral glucose hypometabolism. Impaired glucose metabolism reduces glucose flux through the hexosamine metabolic pathway triggering attenuated O-linked N-acetylglucosamine (O-GlcNAc) protein modification. The goal of the current study was to investigate the link between cognitive function, tau pathology, and O-GlcNAc signaling in an aging mouse model of MetS, agouti KKAy+/- . Male and female C57BL/6, non-agouti KKAy-/- , and agouti KKAy+/- mice were aged 12-18 months on standard chow diet. Body weight, blood glucose, total cholesterol, and triglyceride were measured to confirm the MetS phenotype. Cognition, sensorimotor function, and emotional reactivity were assessed for each genotype followed by plasma and brain tissue collection for biochemical and molecular analyses. Body weight, blood glucose, total cholesterol, and triglyceride levels were significantly elevated in agouti KKAy+/- mice versus C57BL/6 controls and non-agouti KKAy-/- . Behaviorally, agouti KKAy+/- revealed impairments in sensorimotor and cognitive function versus age-matched C57BL/6 and non-agouti KKAy-/- mice. Immunoblotting demonstrated increased phosphorylated tau accompanied with reduced O-GlcNAc protein expression in hippocampal-associated dorsal midbrain of female agouti KKAy+/- versus C57BL/6 control mice. Together, these data demonstrate that impaired cognitive function and AD-related pathology are associated with reduced O-GlcNAc signaling in aging MetS KKAy+/- mice. Overall, our study suggests that interaction of tau pathology with O-GlcNAc signaling may contribute to MetS-induced cognitive dysfunction in aging.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Síndrome Metabólica , Camundongos , Masculino , Feminino , Animais , Proteínas tau/metabolismo , Acetilglucosamina/metabolismo , Glicemia , Camundongos Endogâmicos C57BL , Doença de Alzheimer/metabolismo , Glucose/metabolismo , Modelos Animais de Doenças , Disfunção Cognitiva/etiologia , Envelhecimento , Colesterol
17.
Surgery ; 174(1): 83-90, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37105784

RESUMO

BACKGROUND: Currently, no guidelines exist regarding the appropriate time from diagnosis to treatment among pancreatic adenocarcinoma patients. Herein, we aim to define the median time to treatment in pancreatic adenocarcinoma, factors associated with treatment delay, and prognostic significance. METHODS: We conducted a retrospective study of pancreatic adenocarcinoma patients, stage I-IV, at a tertiary referral center (2017-2020). We subdivided time to treatment (days) into 4 components: (1) Ti: symptom onset to initial provider evaluation, (2) Tii: initial provider evaluation to diagnosis, (3) Tiii: diagnosis to specialist consultation, (4) Tiv: specialist visit to treatment. RESULTS: In total, 217 patients met the inclusion criteria. The median Ti, Tii, Tiii, and Tiv were 20, 12, 4, and 14 days, respectively. The total time to treatment was 75 days. Patients with weight loss had longer Ti (ß = 108.6). More frequent hospitalizations (ß = 19.5) and misdiagnosis (ß = 33.4) were associated with longer Tii. Patients with a history of malignancy (ß = 15) or active treatment of a second disease (ß = 19.4) had longer Tiii. Poor performance status (ß = 6.2) or private insurance (ß = 50.2) were associated with a longer Tiv. Black patients had longer Ti+ii+iii+iv (ß = 100). Time to treatment was not associated with overall survival (P > .05). CONCLUSION: It takes a median time of less than a month for a patient with pancreatic adenocarcinoma to start treatment, even after they visit a primary provider. The greatest opportunity to shorten the overall time to treatment is by having patients seek medical attention earlier (Ti).


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Adenocarcinoma/complicações , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Prognóstico , Estudos Retrospectivos , Neoplasias Pancreáticas
18.
Bone Jt Open ; 4(4): 273-282, 2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37078805

RESUMO

To investigate health-related quality of life (HRQoL) of older adults (aged ≥ 60 years) after tibial plateau fracture (TPF) compared to preinjury and population matched values, and what aspects of treatment were most important to patients. We undertook a retrospective, case-control study of 67 patients at mean 3.5 years (SD 1.3; 1.3 to 6.1) after TPF (47 patients underwent fixation, and 20 nonoperative management). Patients completed EuroQol five-dimension three-level (EQ-5D-3L) questionnaire, Lower Limb Function Scale (LEFS), and Oxford Knee Scores (OKS) for current and recalled prefracture status. Propensity score matching for age, sex, and deprivation in a 1:5 ratio was performed using patient level data from the Health Survey for England to obtain a control group for HRQoL comparison. The primary outcome was the difference in actual (TPF cohort) and expected (matched control) EQ-5D-3L score after TPF. TPF patients had a significantly worse EQ-5D-3L utility (mean difference (MD) 0.09, 95% confidence interval (CI) 0.00 to 0.16; p < 0.001) following their injury compared to matched controls, and had a significant deterioration (MD 0.140, 95% CI 0 to 0.309; p < 0.001) relative to their preoperative status. TPF patients had significantly greater pre-fracture EQ-5D-3L scores compared to controls (p = 0.003), specifically in mobility and pain/discomfort domains. A decline in EQ-5D-3L greater than the minimal important change of 0.105 was present in 36/67 TPF patients (53.7%). Following TPF, OKS (MD -7; interquartile range (IQR) -1 to -15) and LEFS (MD -10; IQR -2 to -26) declined significantly (p < 0.001) from pre-fracture levels. Of the 12 elements of fracture care assessed, the most important to patients were getting back to their own home, having a stable knee, and returning to normal function. TPFs in older adults were associated with a clinically significant deterioration in HRQoL compared to preinjury level and age, sex, and deprivation matched controls for both undisplaced fractures managed nonoperatively and displaced or unstable fractures managed with internal fixation.

19.
Cureus ; 15(2): e35201, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36960263

RESUMO

Thyroid storm is a challenging medical emergency that requires urgent assessment and management in a timely manner. In this article, we report on a case of a 37-year-old female who presented to the emergency department with a thyroid storm complicated by atrial fibrillation (AF) with a rapid ventricular response with no clinical signs of heart failure. As part of her medical management to rate control her AF, she was started on an infusion of a short-acting beta blocker, esmolol, and shortly after, she developed cardiac arrest. This is the second case report published to highlight the significant response (cardiac arrest) of patients with thyroid storm complicated by AF to a low dose esmolol infusion as part of their medical management.

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