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1.
Mayo Clin Proc Digit Health ; 2(1): 119-128, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38577703

RESUMO

Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions. Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty. Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts. Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use.

2.
J Environ Manage ; 356: 120446, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484595

RESUMO

There is a serious concern about the large amount of accumulated plastic waste all around the world. Synthetic polymers such as polyethylene terephthalate (PET), polypropylene (PP), and polyethylene (HDPE, LDPE) are substantially present in the plastic waste generated. There are various methods reported to minimise such plastics waste with certain limitations. To overcome such limitations the present study have been carried out in which thermal decomposition of plastic waste of PET, PP, HDPE, and LDPE studied using a novel plasma pyrolysis reactor. The major objective of this work is to investigate the viability of the continuous plasma pyrolysis process for the treatment of various plastic wastes with respect to waste volume reduction and production of combustible hydrogen-rich fuel gas. The effect of temperature and feed flow rate on product gas yield, product gas efficiency, solid residue yield, and H2/CO ratio has been evaluated. The experiments have been carried out at different temperatures within the range of 700-1000 °C. Plasma pyrolysis system exhibited combustible hydrogen-rich gas as a product and solid residue. Liquid products have not been observed during plasma pyrolysis, unlike conventional pyrolysis. The reaction mechanism of plastic cracking has been discussed based on literature and products obtained in the present work. The effects of feed flow rate and temperature on exergy efficiency were studied using the response surface method. The mass, energy, and exergy analyses have also been carried out for all the experiments, which are in the range of 0.95-0.99, 0.48 to 0.77, and 0.30 to 0.69, respectively.


Assuntos
Plásticos , Polietileno , Polietileno/química , Plásticos/química , Hidrogênio , Pirólise , Polipropilenos/química , Polietilenotereftalatos
3.
Psychosom Med ; 86(4): 289-297, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38436651

RESUMO

OBJECTIVE: To identify distinct sleep health phenotypes in adults, examine transitions in sleep health phenotypes over time, and subsequently relate these to the risk of chronic conditions. METHODS: A national sample of adults from the Midlife in the United States study ( N = 3683) provided longitudinal data with two time points (T1: 2004-2006, T2: 2013-2017). Participants self-reported on sleep health (regularity, satisfaction, alertness, efficiency, duration) and the number and type of chronic conditions. Covariates included age, sex, race, education, education, partnered status, number of children, work status, smoking, alcohol, and physical activity. RESULTS: Latent transition analysis identified four sleep health phenotypes across both time points: good sleepers, insomnia sleepers, weekend catch-up sleepers, and nappers. Between T1 and T2, the majority (77%) maintained their phenotype, with the nappers and insomnia sleepers being the most stable. In fully adjusted models with good sleepers at both time points as the reference, being an insomnia sleeper at either time point was related to having an increased number of total chronic conditions by 28%-81% at T2, adjusting for T1 conditions. Insomnia sleepers at both time points were at 72%-188% higher risk for cardiovascular disease, diabetes, depression, and frailty. Being a napper at any time point related to increased risks for diabetes, cancer, and frailty. Being a weekend catch-up sleeper was not associated with chronic conditions. Those with lower education and unemployed were more likely to be insomnia sleepers; older adults and retirees were more likely to be nappers. CONCLUSION: Findings indicate a heightened risk of chronic conditions involved in suboptimal sleep health phenotypes, mainly insomnia sleepers.


Assuntos
Fenótipo , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Feminino , Pessoa de Meia-Idade , Doença Crônica , Estudos Longitudinais , Idoso , Estados Unidos/epidemiologia , Adulto
4.
Leuk Lymphoma ; 65(5): 638-646, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38315613

RESUMO

T cell dyscrasias that demonstrate a proclivity for the subcutaneous fat include atypical lymphocytic lobular panniculitis, lupus profundus, and primary subcutaneous T cell lymphoma, including subcutaneous panniculitis-like T cell lymphoma (SPTCL). We encountered two patients who developed fever and indurated abdominal erythema at their peginterferon alfa-2a injection sites. Biopsies showed an atypical CD8 positive, granzyme positive, CD5 negative, MXA negative lymphocytic lobular panniculitis, diagnostic of SPTCL. Peginterferon alfa-2a was held in both patients. One patient received chemotherapy with an excellent response, while the other continued to have progressive disease. Peginterferon alfa-2a is known to significantly elevate serum MXA, which may induce high levels of MXA expression at the injection site, creating a microenvironment for the development of lupus profundus, which may eventuate into SPTCL. In summation, a potential risk of peginterferon alfa-2a injections is the development of SPTCL potentially arising in a background of an exogenous interferon triggered lymphocytic panniculitis.


Assuntos
Interferon-alfa , Linfoma de Células T , Paniculite , Polietilenoglicóis , Proteínas Recombinantes , Humanos , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/administração & dosagem , Interferon-alfa/efeitos adversos , Interferon-alfa/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Paniculite/induzido quimicamente , Paniculite/diagnóstico , Paniculite/patologia , Paniculite/etiologia , Feminino , Linfoma de Células T/diagnóstico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/patologia , Pessoa de Meia-Idade , Masculino , Biópsia , Adulto
6.
Am J Ophthalmol Case Rep ; 34: 102003, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38384737

RESUMO

Purpose: Trabeculectomy surgery is a commonly performed procedure for treatment of glaucoma. While the goal is to lower intraocular pressure, over-filtration may cause hypotony with ocular structural changes and vision loss. Observations: A 53-year-old woman with primary open-angle glaucoma was referred to our service for further evaluation. The patient previously underwent trabeculectomy 9 years prior and was found to have a cataract and hypotony maculopathy in the right eye. Treatment options included cataract surgery alone, bleb revision alone, or combined cataract extraction and bleb revision. Biometry revealed corneal astigmatism in the right eye, and significant disparity in axial length between the two eyes. Since the axial length and corneal astigmatic changes were presumed to be at least partially reversible, measurements from the non-operative left eye influenced the lens selection for the hypotonous right eye. The patient underwent combined phacoemulsification and bleb revision. While IOP increased and hypotony was partly reversed, there was hyperopic and astigmatic refractive surprise after surgery.The patient subsequently underwent intraocular lens exchange using biometric values of the previously hypotonous eye and met the target post-operative refractive goal. Conclusions and importance: This case demonstrates changes to the axial length and ocular structure following longstanding hypotony maculopathy may be permanent, even after restoration of normotensive intraocular pressure.

7.
PLoS Pathog ; 20(1): e1011881, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38190392

RESUMO

In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKÆ´ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.


Assuntos
Infecções por HIV , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/fisiologia , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Proteínas WT1/genética , Proteínas WT1/metabolismo , Células Endoteliais/metabolismo , Infecções por HIV/metabolismo , Isoformas de Proteínas/metabolismo , Microambiente Tumoral
8.
Sci Rep ; 14(1): 1620, 2024 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238404

RESUMO

The microbial biotransformation using low-cost feedstock to produce biopolymers (degradable), an alternative to petrochemical-based synthesis plastics (non-degradable), can be a beneficial approach towards sustainable development. In this study, the dairy industry processes waste (whey) is used in polyhydroxyalkanoate (PHA) copolymer production. Initial screening suggested that Ralstonia eutropha produced higher PHA as compared to Bacillus megaterium. A central composite rotatable design-based optimization using two process variables (amino acid and tween-80) concentration remarkably influenced PHA co-polymer production under physiological conditions of pH (7), temperature (37 °C), and agitation rate of 150 rpm. High polyhydroxybutyrate (PHB) mass fraction yield of 69.3% was observed as compared to predicted yield of 62.8% from deproteinized whey as feed. The combination of tryptophan (50 mg L-1) and tween-80 (3 mL-1) enhanced R. eutropha mass gain to 6.80 g L-1 with PHB contents of 4.71 g L-1. Further, characterization of PHA and its copolymers was done by ESI-MS, FTIR, and TEM. On upscaling up to 3.0 L, the PHA contents and yields were noted as quite similar by R. eutropha. This study demonstrates that dairy waste processing waste can be potentially utilized as inexpensive feed for producing high content of biopolymers to develop a sustainable system of waste management.


Assuntos
Poli-Hidroxialcanoatos , Polissorbatos , Poli-Hidroxialcanoatos/química , Biopolímeros , Aminoácidos , Plásticos
9.
JAC Antimicrob Resist ; 6(1): dlad142, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38161969

RESUMO

Background: High-quality systematic data on antimicrobial use in UK inpatient paediatric haematology-oncology services are lacking, despite this population being at high risk from antimicrobial exposure and resistance. Objectives: We conducted a retrospective study to demonstrate how routinely collected electronic prescribing data can address this issue. Patients and methods: This retrospective study describes and compares IV antibiotic consumption between two UK paediatric haematology-oncology inpatient units, between 2018 and 2022. Both sites provide similar services and receive proactive antimicrobial stewardship input. Data were extracted from each site's antimicrobial surveillance system, which report monthly days of therapy (DOT) per 100 patient-days (PD). Consumption was reported for specific and total antibiotics. Trends were modelled using linear regression and autoregressive moving average models. Results: Total IV antibiotic consumption at each site was similar. Median monthly DOT per 100 PD were 25.9 (IQR: 22.1-34.0) and 29.4 (24.2-34.9). Total antibiotic use declined at both sites, with estimated annual yearly reductions of 3.52 DOT per 100 PD (95% CI: 0.46-6.59) and 2.57 (1.30-3.85). Absolute consumption was similar for carbapenems, piperacillin/tazobactam and aminoglycosides, whilst ceftriaxone and teicoplanin demonstrated approximately 3-fold relative differences in median monthly consumption. Meropenem, piperacillin/tazobactam, teicoplanin, vancomycin and gentamicin all demonstrated statistically significant reductions in use over time at either one or both sites, although this was most marked for piperacillin/tazobactam and vancomycin. Conclusions: Routinely collected electronic prescribing data can aid benchmarking of antibiotic use in paediatric haematology-oncology inpatients, highlighting areas to target stewardship strategies, and evaluating their impact. This approach should be rolled out nationally, and to other high-risk groups.

10.
Cornea ; 43(4): 425-431, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37506362

RESUMO

PURPOSE: The aim of this study was to report the outcomes of graft fixation using interrupted, full-thickness sutures on graft detachment after Descemet stripping endothelial keratoplasty (DSEK). METHODS: All DSEK procedures performed at Mayo Clinic, Rochester, MN, from 2015 through 2022 were retrospectively reviewed. Risk factors for graft detachment were defined as previous incisional glaucoma surgery, previous penetrating keratoplasty, or absence of the normal lens-capsule barrier. Cases were categorized into sutured, high-risk grafts; unsutured, high-risk grafts; and unsutured, low-risk grafts. The primary outcome was graft detachment, and secondary outcomes were early graft failure and graft clarity at 12 months after surgery. RESULTS: Demographics between the high-risk groups were similar for sex and age at the time of surgery. Graft detachment occurred in 4 of 97 sutured, high-risk eyes (4.1%) and 24 of 119 unsutured high-risk eyes (20.2%) ( P = 0.002). In comparison, graft detachment occurred in 18 of 181 unsutured low-risk eyes (9.9%). The incidence of early graft failure was 2.1%, 5.0%, and 3.3% and late graft failure by 12 months was 9.8%, 12.8%, and 4.2%, respectively. CONCLUSIONS: In eyes with high-risk factors for graft detachment, suture fixation of the graft in DSEK decreased graft detachment to a rate at least as low as that in low-risk eyes.


Assuntos
Doenças da Córnea , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Humanos , Estudos Retrospectivos , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Lâmina Limitante Posterior/cirurgia , Ceratoplastia Penetrante/métodos , Suturas , Sobrevivência de Enxerto , Doenças da Córnea/cirurgia , Endotélio Corneano/cirurgia
11.
Pathobiology ; 91(1): 18-29, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36944324

RESUMO

Somatic mutations in the nucleophosmin (NPM1) gene occur in approximately 30% of de novo acute myeloid leukemias (AMLs) and are relatively enriched in normal karyotype AMLs. Earlier World Health Organization (WHO) classification schema recognized NPM1-mutated AMLs as a unique subtype of AML, while the latest WHO and International Consensus Classification (ICC) now consider NPM1 mutations as AML-defining, albeit at different blast count thresholds. NPM1 mutational load correlates closely with disease status, particularly in the post-therapy setting, and therefore high sensitivity-based methods for detection of the mutant allele have proven useful for minimal/measurable residual disease (MRD) monitoring. MRD status has been conventionally measured by either multiparameter flow cytometry (MFC) and/or molecular diagnostic techniques, although recent data suggest that MFC data may be potentially more challenging to interpret in this AML subtype. Of note, MRD status does not predict patient outcome in all cases, and therefore a deeper understanding of the biological significance of MRD may be required. Recent studies have confirmed that NPM1-mutated cells rely on overexpression of HOX/MEIS1, which is dependent on the presence of the aberrant cytoplasmic localization of mutant NPM1 protein (NPM1c); this biology may explain the promising response to novel agents, including menin inhibitors and second-generation XPO1 inhibitors. In this review, these and other recent developments around NPM1-mutated AML, in addition to open questions warranting further investigation, will be discussed.


Assuntos
Leucemia Mieloide Aguda , Nucleofosmina , Humanos , Alelos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutação , Proteínas Nucleares/genética
13.
Urol Oncol ; 42(4): 116.e17-116.e21, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38087711

RESUMO

BACKGROUND: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. METHODS: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. RESULTS: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. CONCLUSIONS: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic.


Assuntos
COVID-19 , Neoplasias da Bexiga Urinária , Humanos , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Vacina BCG/uso terapêutico , COVID-19/epidemiologia , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Pandemias , Saúde Pública , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/tratamento farmacológico
14.
Artigo em Inglês | MEDLINE | ID: mdl-37950462

RESUMO

BACKGROUND: Having multiple sleep problems is common in adulthood. Yet, most studies have assessed single sleep variables at one timepoint, potentially misinterpreting health consequences of co-occurring sleep problems that may change over time. We investigated the relationship between multidimensional sleep health across adulthood and mortality. METHODS: Participants from the Midlife in the United States Study reported sleep characteristics in 2004-2006 (MIDUS-2; M2) and in 2013-2014 (MIDUS-3; M3). We calculated a composite score of sleep health problems across 5 dimensions: Regularity, Satisfaction, Alertness, Efficiency, and Duration (higher = more problems). Two separate models for baseline sleep health (n = 5 140; median follow-up time = 15.3 years) and change in sleep health (n = 2 991; median follow-up time = 6.4 years) to mortality were conducted. Cox regression models controlled for sociodemographics and key health risk factors (body mass index, smoking, depressive symptoms, diabetes, and hypertension). RESULTS: On average, 88% of the sample reported having one or more sleep health problems at M2. Each additional sleep health problem at M2 was associated with 12% greater risk of all-cause mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.04-1.21), but not heart disease-related mortality (HR = 1.14, 95% CI = 0.99-1.31). An increase in sleep health problems from M2 to M3 was associated with 27% greater risk of all-cause mortality (HR = 1.27, 95% CI = 1.005-1.59), and 153% greater risk of heart disease mortality (HR = 2.53, 95% CI = 1.37-4.68). CONCLUSIONS: More sleep health problems may increase the risk of early mortality. Sleep health in middle and older adulthood is a vital sign that can be assessed at medical checkups to identify those at greater risk.


Assuntos
Hipertensão , Transtornos do Sono-Vigília , Humanos , Estados Unidos/epidemiologia , Idoso , Sono , Fatores de Risco , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia
15.
Res Sq ; 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38045314

RESUMO

Percutaneous renal biopsy (PRB) is commonly used for kidney cancer diagnosis. However, current PRB remains challenging in sampling accuracy. This study introduces a forward-viewing optical coherence tomography (OCT) probe for differentiating tumor and normal tissues, aiming at precise PRB guidance. Five human kidneys and renal carcinoma samples were used to evaluate the performance of our probe. Based on their distinct OCT imaging features, tumor and normal renal tissues can be accurately distinguished. We examined the attenuation coefficient for tissue classification and achieved 98.19% tumor recognition accuracy, but underperformed for distinguishing normal tissues. We further developed convolutional neural networks (CNN) and evaluated two CNN architectures: ResNet50 and InceptionV3, yielding 99.51% and 99.48% accuracies for tumor recognition, and over 98.90% for normal tissues recognition. In conclusion, combining OCT and CNN significantly enhanced the PRB guidance, offering a promising guidance technology for improved kidney cancer diagnosis.

16.
Clin Ther ; 45(11): 1047-1054, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37709601

RESUMO

PURPOSE: Despite an increase in treatment options, and substantial reductions in cardiovascular mortality over the past half-century, atherosclerosis remains the most prevalent cause of premature mortality worldwide. The development of innovative new therapies is crucial to further minimize atherosclerosis-related deaths. The diverse array of cell phenotypes derived from vascular smooth muscle cells (SMCs) and macrophages within atherosclerotic plaques are increasingly becoming recognized for their beneficial and detrimental roles in plaque stability and disease burden. This review explores how contemporary transcriptomics and fate-mapping studies have revealed vascular cell plasticity as a relatively unexplored target for therapeutic intervention. METHODS: Recent literature for this narrative review was obtained by searching electronic databases (ie, Google Scholar, PubMed). Additional studies were sourced from reference lists and the authors' personal databases. FINDINGS: The lipid-rich and inflammatory plaque milieu induces SMC phenotypic switching to both beneficial and detrimental phenotypes. Likewise, macrophage heterogeneity increases with disease burden to a variety of pro-inflammatory and anti-inflammatory activation states. These vascular cell phenotypes are determinants of plaque structure stability, and it is therefore highly likely that they influence clinical outcomes. Development of clinical treatments targeting deleterious phenotypes or promoting pro-healing phenotypes remains in its infancy. However, existing treatments (statins) have shown beneficial effects toward macrophage polarization, providing a rationale for more targeted approaches. In contrast, beneficial SMC phenotypic modulation with these pharmacologic agents has yet to be achieved. The range of modulated vascular cell phenotypes provides a multitude of novel targets and the potential to reduce future adverse events. IMPLICATIONS: Vascular cell phenotypic heterogeneity must continue to be explored to lower cardiovascular events in the future. The rapidly increasing weight of evidence surrounding the role of SMC plasticity and macrophage polarity in plaque vulnerability provides a strong foundation upon which development of new therapeutics must follow. This approach may prove to be crucial in reducing cardiovascular events and improving patient benefit in the future.


Assuntos
Aterosclerose , Placa Aterosclerótica , Humanos , Músculo Liso Vascular/metabolismo , Plasticidade Celular , Aterosclerose/tratamento farmacológico , Macrófagos , Fenótipo
17.
Blood ; 142(26): 2282-2295, 2023 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-37774374

RESUMO

ABSTRACT: The spatial anatomy of hematopoiesis in the bone marrow (BM) has been extensively studied in mice and other preclinical models, but technical challenges have precluded a commensurate exploration in humans. Institutional pathology archives contain thousands of paraffinized BM core biopsy tissue specimens, providing a rich resource for studying the intact human BM topography in a variety of physiologic states. Thus, we developed an end-to-end pipeline involving multiparameter whole tissue staining, in situ imaging at single-cell resolution, and artificial intelligence-based digital whole slide image analysis and then applied it to a cohort of disease-free samples to survey alterations in the hematopoietic topography associated with aging. Our data indicate heterogeneity in marrow adipose tissue (MAT) content within each age group and an inverse correlation between MAT content and proportions of early myeloid and erythroid precursors, irrespective of age. We identify consistent endosteal and perivascular positioning of hematopoietic stem and progenitor cells (HSPCs) with medullary localization of more differentiated elements and, importantly, uncover new evidence of aging-associated changes in cellular and vascular morphologies, microarchitectural alterations suggestive of foci with increased lymphocytes, and diminution of a potentially active megakaryocytic niche. Overall, our findings suggest that there is topographic remodeling of human hematopoiesis associated with aging. More generally, we demonstrate the potential to deeply unravel the spatial biology of normal and pathologic human BM states using intact archival tissue specimens.


Assuntos
Inteligência Artificial , Células-Tronco Hematopoéticas , Humanos , Camundongos , Animais , Células-Tronco Hematopoéticas/patologia , Medula Óssea/patologia , Hematopoese/fisiologia , Envelhecimento
18.
Polymers (Basel) ; 15(18)2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37765522

RESUMO

The production of renewable energy or biochemicals is gaining more attention to minimize the emissions of greenhouse gases such as methane (CH4) and carbon dioxide for sustainable development. In the present study, the influence of copper (Cu)- and iron (Fe)-based nanoparticles (NPs), such as Cu, Fe3O4, and CuFe2O4, was evaluated during the growth of methanotrophs for inoculum preparation and on the development of a polymeric-matrix-based encapsulation system to enhance methanol production from simulated biogas (CH4 and CO2). The use of simulated biogas feed and the presence of NP-derived inoculums produce a remarkable enhancement in methanol production up to 149% and 167% for Methyloferula stellata and Methylocystis bryophila free-cells-based bioconversion, respectively, compared with the use of pure CH4 as a control feed during the growth stage. Furthermore, these methanotrophs encapsulated within a polymeric matrix and NPs-based systems exhibited high methanol production of up to 156%, with a maximum methanol accumulation of 12.8 mmol/L over free cells. Furthermore, after encapsulation, the methanotrophs improved the stability of residual methanol production and retained up to 62.5-fold higher production potential than free cells under repeated batch reusability of 10 cycles. In the presence of CH4 vectors, methanol production by M. bryophila improved up to 16.4 mmol/L and retained 20% higher recycling stability for methanol production in paraffin oil. These findings suggest that Cu and Fe NPs can be beneficially employed with a polymeric matrix to encapsulate methanotrophs and improve methanol production.

19.
Antioxidants (Basel) ; 12(7)2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37507952

RESUMO

Quinoa (Chenopodium quinoa Willd) and chia (Salvia hispanica) are essential traditional crops with excellent nutritional properties. Quinoa is known for its high and good quality protein content and nine essential amino acids vital for an individual's development and growth, whereas chia seeds contain high dietary fiber content, calories, lipids, minerals (calcium, magnesium, iron, phosphorus, and zinc), and vitamins (A and B complex). Chia seeds are also known for their presence of a high amount of omega-3 fatty acids. Both quinoa and chia seeds are gluten-free and provide medicinal properties due to bioactive compounds, which help combat various chronic diseases such as diabetes, obesity, cardiovascular diseases, and metabolic diseases such as cancer. Quinoa seeds possess phenolic compounds, particularly kaempferol, which can help prevent cancer. Many food products can be developed by fortifying quinoa and chia seeds in different concentrations to enhance their nutritional profile, such as extruded snacks, meat products, etc. Furthermore, it highlights the value-added products that can be developed by including quinoa and chia seeds, alone and in combination. This review focused on the recent development in quinoa and chia seeds nutritional, bioactive properties, and processing for potential human health and therapeutic applications.

20.
Biomedicines ; 11(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37371705

RESUMO

Cancer is a significant challenge for effective treatment due to its complex mechanism, different progressing stages, and lack of adequate procedures for screening and identification. Pancreatic cancer is typically identified in its advanced progression phase with a low survival of ~5 years. Among cancers, pancreatic cancer is also considered a high mortality-causing casualty over other accidental or disease-based mortality, and it is ranked seventh among all mortality-associated cancers globally. Henceforth, developing diagnostic procedures for its early detection, understanding pancreatic cancer-linked mechanisms, and various therapeutic strategies are crucial. This review describes the recent development in pancreatic cancer progression, mechanisms, and therapeutic approaches, including molecular techniques and biomedicines for effectively treating cancer.

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