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1.
Cell ; 187(8): 1834-1852.e19, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38569543

RESUMO

Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition. Integrated analysis revealed microbial pathways implicated in CVD, including flavonoid, γ-butyrobetaine, and cholesterol metabolism. Species from the Oscillibacter genus were associated with decreased fecal and plasma cholesterol levels. Using functional prediction and in vitro characterization of multiple representative human gut Oscillibacter isolates, we uncovered conserved cholesterol-metabolizing capabilities, including glycosylation and dehydrogenation. These findings suggest that cholesterol metabolism is a broad property of phylogenetically diverse Oscillibacter spp., with potential benefits for lipid homeostasis and cardiovascular health.


Assuntos
Bactérias , Doenças Cardiovasculares , Colesterol , Microbioma Gastrointestinal , Humanos , Bactérias/metabolismo , Doenças Cardiovasculares/metabolismo , Colesterol/análise , Colesterol/sangue , Colesterol/metabolismo , Fezes/química , Estudos Longitudinais , Metaboloma , Metabolômica , RNA Ribossômico 16S/metabolismo
2.
PLoS Comput Biol ; 20(4): e1012022, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38607982

RESUMO

The Patient Similarity Network paradigm implies modeling the similarity between patients based on specific data. The similarity can summarize patients' relationships from high-dimensional data, such as biological omics. The end PSN can undergo un/supervised learning tasks while being strongly interpretable, tailored for precision medicine, and ready to be analyzed with graph-theory methods. However, these benefits are not guaranteed and depend on the granularity of the summarized data, the clarity of the similarity measure, the complexity of the network's topology, and the implemented methods for analysis. To date, no patient classifier fully leverages the paradigm's inherent benefits. PSNs remain complex, unexploited, and meaningless. We present StellarPath, a hierarchical-vertical patient classifier that leverages pathway analysis and patient similarity concepts to find meaningful features for both classes and individuals. StellarPath processes omics data, hierarchically integrates them into pathways, and uses a novel similarity to measure how patients' pathway activity is alike. It selects biologically relevant molecules, pathways, and networks, considering molecule stability and topology. A graph convolutional neural network then predicts unknown patients based on known cases. StellarPath excels in classification performances and computational resources across sixteen datasets. It demonstrates proficiency in inferring the class of new patients described in external independent studies, following its initial training and testing phases on a local dataset. It advances the PSN paradigm and provides new markers, insights, and tools for in-depth patient profiling.


Assuntos
Biologia Computacional , Medicina de Precisão , Humanos , Biologia Computacional/métodos , Medicina de Precisão/métodos , Redes Neurais de Computação , Algoritmos , Genômica/métodos , Biomarcadores/metabolismo , Perfilação da Expressão Gênica/métodos , Proteômica/métodos , Multiômica
3.
Nano Lett ; 24(26): 7979-7986, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829309

RESUMO

Magnetic anisotropy in atomically thin correlated heterostructures is essential for exploring quantum magnetic phases for next-generation spintronics. Whereas previous studies have mostly focused on van der Waals systems, here we investigate the impact of dimensionality of epitaxially grown correlated oxides down to the monolayer limit on structural, magnetic, and orbital anisotropies. By designing oxide superlattices with a correlated ferromagnetic SrRuO3 and nonmagnetic SrTiO3 layers, we observed modulated ferromagnetic behavior with the change of the SrRuO3 thickness. Especially, for three-unit-cell-thick layers, we observe a significant 1500% improvement of the coercive field in the anomalous Hall effect, which cannot be solely attributed to the dimensional crossover in ferromagnetism. The atomic-scale heterostructures further reveal the systematic modulation of anisotropy for the lattice structure and orbital hybridization, explaining the enhanced magnetic anisotropy. Our findings provide valuable insights into engineering the anisotropic hybridization of synthetic magnetic crystals, offering a tunable spin order for various applications.

4.
Proteomics ; 24(11): e2300089, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38168906

RESUMO

Much recent research has been dedicated to exploring the utility of extracellular vesicles (EVs) as circulating disease biomarkers. Underpinning this work is the assumption that the molecular cargo of EVs directly reflects the originating cell. Few attempts have been made, however, to empirically validate this on the -omic level. To this end, we have performed an integrative multi-omic analysis of a panel of breast cancer cell lines and corresponding EVs. Whole transcriptome analysis validated that the cellular transcriptome remained stable when cultured cells are transitioned to low serum or serum-free medium for EV collection. Transcriptomic profiling of the isolated EVs indicated a positive correlation between transcript levels in cells and EVs, including disease-associated transcripts. Analysis of the EV proteome verified that HER2 protein is present in EVs, however neither the estrogen (ER) nor progesterone (PR) receptor proteins are detected regardless of cellular expression. Using multivariate analysis, we derived an EV protein signature to infer cellular patterns of ER and HER2 expression, though the ER protein could not be directly detected. Integrative analyses affirmed that the EV proteome and transcriptome captured key phenotypic hallmarks of the originating cells, supporting the potential of EVs for non-invasive monitoring of breast cancers.


Assuntos
Neoplasias da Mama , Vesículas Extracelulares , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Feminino , Proteômica/métodos , Linhagem Celular Tumoral , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Proteoma/análise , Proteoma/metabolismo , Perfilação da Expressão Gênica/métodos , Transcriptoma , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Receptores de Estrogênio/metabolismo , Multiômica
5.
BMC Bioinformatics ; 25(1): 64, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331751

RESUMO

Functional analysis of high throughput experiments using pathway analysis is now ubiquitous. Though powerful, these methods often produce thousands of redundant results owing to knowledgebase redundancies upstream. This scale of results hinders extensive exploration by biologists and can lead to investigator biases due to previous knowledge and expectations. To address this issue, we present vissE, a flexible network-based analysis and visualisation tool that organises information into semantic categories and provides various visualisation modules to characterise them with respect to the underlying data, thus providing a comprehensive view of the biological system. We demonstrate vissE's versatility by applying it to three different technologies: bulk, single-cell and spatial transcriptomics. Applying vissE to a factor analysis of a breast cancer spatial transcriptomic data, we identified stromal phenotypes that support tumour dissemination. Its adaptability allows vissE to enhance all existing gene-set enrichment and pathway analysis workflows, empowering biologists during molecular discovery.


Assuntos
Neoplasias da Mama , Perfilação da Expressão Gênica , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Transcriptoma , Fenótipo
6.
Strahlenther Onkol ; 200(7): 624-632, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38315236

RESUMO

BACKGROUND: Radiotherapy is one of the main treatment options for patients with esophageal cancer; however, it has been linked with an increased risk of cardiac toxicities. In the current study, we evaluated the effect of planning the radiation in deep-inspiration breath hold (DIBH) on the dose sparing of cardiac substructures and lung. MATERIALS AND METHODS: In this study, we analyzed 30 radiation therapy plans from 15 patients diagnosed with esophageal cancer planned for neoadjuvant radiotherapy. Radiation plans were generated for 41.4 Gy and delivered in 1.8 Gy per fraction for free-breathing (FB) and DIBH techniques. We then conducted a comparative dosimetric analysis, evaluating target volume coverage, the impact on cardiac substructures, and lung doses across the two planning techniques for each patient. RESULTS: There was no significant disparity in target volume dose coverage between DIBH and FB plans. However, the Dmean, D2%, and V30% of the heart experienced substantial reductions in DIBH relative to FB, with values of 6.21 versus 7.02 Gy (p = 0.011), 35.28 versus 35.84 Gy (p = 0.047), and 5% versus 5.8% (p = 0.048), respectively. The Dmean of the left ventricle was notably lower in DIBH compared to FB (4.27 vs. 5.12 Gy, p = 0.0018), accompanied by significant improvements in V10. Additionally, the Dmean and D2% of the left coronary artery, as well as the D2% of the right coronary artery, were significantly lower in DIBH. The dosimetric impact of DIBH on cardiac substructures proved more advantageous for middle esophageal (ME) than distal esophageal (DE) tumors. CONCLUSION: Radiotherapy in DIBH could provide a method to reduce the radiation dose to the left ventricle and coronaries, which could reduce the cardiac toxicity of the modality.


Assuntos
Suspensão da Respiração , Neoplasias Esofágicas , Coração , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Humanos , Neoplasias Esofágicas/radioterapia , Masculino , Feminino , Coração/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Pessoa de Meia-Idade , Órgãos em Risco/efeitos da radiação , Idoso , Lesões por Radiação/prevenção & controle , Lesões por Radiação/etiologia , Terapia Neoadjuvante , Radiometria
7.
Strahlenther Onkol ; 200(8): 715-724, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38689147

RESUMO

PURPOSE: Hepatocellular carcinoma (HCC) poses a unique challenge due to its predilection for developing on compromised livers, often limiting surgical options. Stereotactic body radiotherapy (SBRT) has emerged as a promising local treatment modality for HCC. This study aims to assess the effectiveness of SBRT in HCC patients not suitable for surgery, focusing on local control, optimal radiation dosing, and prognostic factors. METHODS: In this retrospective analysis, 52 HCC patients treated with SBRT were examined. The study assessed local control, progression-free survival (PFS), and overall survival (OS) while conducting dosimetric analyses. The relationship between mean liver dose and Child-Pugh score (CPS) progression was also explored. RESULTS: SBRT demonstrated 93.4% freedom from local progression (FFLP) at 12 months. Notably, a near minimum dose (D98%) below 61 Gy as an equivalent dose in 2­Gy fractions with α/ß 10 Gy (EQD2α/ß10) was associated with reduced FFLP (p-value 0.034). Logistic regression analysis revealed a dose-response relationship for FFLP and D98% with 95% and 98% probability of FFLP at a dose of 56.9 and 73.1 Gy, respectively. The study observed OS rates of 63.7% at 1 year and 34.3% at 3 years. Patients with portal vein tumor thrombus (PVTT) and larger tumors (≥ 37 cm3) experienced decreased PFS and OS. Multivariate analysis identified PVTT, larger tumor volume, and performance status as independent predictors of reduced OS. Notably, classical radiation-induced disease (cRILD) was absent, but nonclassical (nc) RILD occurred in 7.7% of patients. Regression analysis linked a mean EQD2α/ß3-8 dose to the liver (12.8-12.6) with a 10% likelihood of ncRILD. CONCLUSION: SBRT offers a compelling option for achieving high local control and promising survival outcomes in HCC. The study supports a radiation dose range of 61-73.1 Gy, coupled with a mean liver dose under 12.6-12.8 Gy as EQD2, to achieve favorable FFLP rates, with acceptable toxicity rates.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radiocirurgia , Humanos , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Radiocirurgia/métodos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Idoso de 80 Anos ou mais , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Adulto , Intervalo Livre de Progressão , Prognóstico
8.
Langmuir ; 40(18): 9797-9808, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38669636

RESUMO

In this study, we report the modification of flexible copper films via the spontaneous reduction of aryldiazonium gold salts [X-4-C6H4N≡N]AuCl4 (X═COOH, NO2). The electroless modification involves dipping of flexible copper films in the aryldiazonium gold solutions for a few seconds, under ambient conditions, followed by a washing step with deionized water to obtain a mechanically robust gold-aryl coating. The chemical composition, morphology, electronic structure, and optical properties of the gold-aryl layer and the flexibility of the modified copper films are supported by the results from X-ray photoelectron spectroscopy (XPS), electrochemistry, contact angle, scanning electron microscopy (SEM), and ultraviolet photoelectron spectroscopy (UPS). XPS surface analysis showed metallic gold in addition to C-C, C-O/C-N, and C═O functional groups from the grafted aryls. Cu 2p showed metallic copper as a major component and a small amount of Cu(II) ions. Wettability studies showed that Au-COOH@Cu increased the contact angle of the bare copper films from 68.0 ± 0.7° to 82.0° ± 0.7°, while Au-NO2@Cu increased the contact angle to 134.0° ± 0.3°. UPS energy profile analysis of [HOOC-4-C6H4N≡N]AuCl4 (valence band maximum = 1.91 eV) exhibited greater reducibility than [O2N-4-C6H4N≡N]AuCl4 (valence band maximum = 2.91 eV). The lower ionization potential of [HOOC-4-C6H4N≡N]AuCl4 (IP = 4.33 eV) enhanced the reactivity upon copper film contact, potentially inducing efficient energy level alignment, compared with [O2N-4-C6H4N≡N]AuCl4 (IP = 5.62 eV). UPS results were further supported by electrochemistry investigation which revealed that [HOOC-4-C6H4N≡N]AuCl4 is easily reducible compared with [O2N-4-C6H4N≡N]AuCl4. The findings presented here hold significant implications for developing flexible copper films and pave the way for future advancements in electronic material modification for industrial applications.

9.
Langmuir ; 40(33): 17675-17688, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39120713

RESUMO

The performance of gold nanospheres as substrates for surface-enhanced Raman spectroscopy (SERS) investigation has been compromised by their low adsorption efficiency, high colloidal dispersibility, and diminishing hot spots. However, gold nanosphere substrates modified using aryldiazonium gold(III) chemistry via durable gold-carbon bonds are promising for SERS enhancement due to their controlled organic layer density. In this study, arylated gold nanospheres AuNSs-COOH have shown SERS enhancement when incorporated into graphene oxide (GO) to form nanocomposites (NCs) labeled AuNSs-COOH/GO (AuNCs). Our investigation using X-ray photoelectron spectroscopy (XPS) surface analysis showed that the gold-aryl nanospheres reached their maximum SERS enhancement with an optimal coating. The evaluation included the Au 4f chemical environment and compact graphitic layers for the SERS substrate optimization. The fabricated AuNC substrates demonstrated superior efficiency and reproducibility. A broad linear range of 10-3-10-7 M 4-nitrophenol detection was obtained with exceptional repeatability, as evidenced by the relative standard deviation (RSD) of 9.32%. A detailed investigation of the energy profiles, particularly the valence band maximum (VBM) and band gap values of the substrate and analyte, depicted the electromagnetic (EM) and charge-transfer-induced enhancement and the role of GO inclusion in substrate efficiency in SERS enhancement mechanisms. The finite-difference time domain (FDTD) simulation results revealed that AuNCs incorporated with graphitic nanostructures exhibited the most substantial SERS effect through an EM field enhancement mechanism. This study demonstrated significant SERS enhancement using gold-aryl nanospheres when modified with GO, in contrast to the typical reliance on anisotropic nanostructures.

10.
World J Urol ; 42(1): 392, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985346

RESUMO

OBJECTIVE: We sought to prospectively evaluate the impact of previously failed SWL on subsequent URS outcomes in the treatment of upper urinary tract stones. MATERIALS AND METHODS: Between May 2021 and May 2023, one hundred thirty-six patients with proximal ureteral stones < 1.5 cm and renal stones < 2.5 cm who were candidates for URS were prospectively assigned to a non-SWL group, which included patients without a history of failed SWL before URS, and a post-SWL group, which included patients with a history of failed SWL before URS. The success rate was the primary outcome. The perioperative data of the two groups were compared. RESULTS: The stone-free rate was 83.3% in the post-SWL group versus 81.3% in the non-SWL group, and 8.3% in the post-SWL group versus 9.4% in the non-SWL group had clinically insignificant residual fragments. There was no significant difference in the stone-free rate or success rate between the groups. No significant differences in intraoperative fluoroscopy time, operative time, intraoperative stone appearance, perioperative complications, or the presence of embedded fragments in the ureteral mucosa were detected between the two groups. CONCLUSION: Compared with patients who underwent primary URS, patients who underwent salvage URS for upper urinary tract stones had similar stone-free rates, success rates, operative times, fluoroscopy times, and complication rates without any significant differences.


Assuntos
Cálculos Renais , Litotripsia , Falha de Tratamento , Cálculos Ureterais , Ureteroscopia , Humanos , Estudos Prospectivos , Feminino , Litotripsia/métodos , Ureteroscopia/métodos , Masculino , Pessoa de Meia-Idade , Cálculos Ureterais/terapia , Cálculos Ureterais/cirurgia , Cálculos Renais/cirurgia , Cálculos Renais/terapia , Adulto , Resultado do Tratamento , Idoso
11.
Arch Virol ; 169(5): 95, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594485

RESUMO

The first detection of a human infection with avian influenza A/H6N1 virus in Taiwan in 2013 has raised concerns about this virus. During our routine surveillance of avian influenza viruses (AIVs) in live-bird markets in Egypt, an H6N1 virus was isolated from a garganey duck and was characterized. Phylogenetic analysis indicated that the Egyptian H6N1 strain A/Garganey/Egypt/20869C/2022(H6N1) has a unique genomic constellation, with gene segments inherited from different subtypes (H5N1, H3N8, H7N3, H6N1, and H10N1) that have been detected previously in AIVs from Egypt and some Eurasian countries. We examined the replication of kinetics of this virus in different mammalian cell lines (A549, MDCK, and Vero cells) and compared its pathogenicity to that of the ancestral H6N1 virus A/Quail/HK/421/2002(H6N1). The Egyptian H6N1 virus replicated efficiently in C57BL/6 mice without prior adaptation and grew faster and reached higher titers than in A549 cells than the ancestral strain. These results show that reassortant H6 AIVs might pose a potential threat to human health and highlight the need to continue surveillance of H6 AIVs circulating in nature.


Assuntos
Vírus da Influenza A Subtipo H3N8 , Virus da Influenza A Subtipo H5N1 , Vírus da Influenza A , Influenza Aviária , Animais , Camundongos , Chlorocebus aethiops , Humanos , Influenza Aviária/epidemiologia , Egito/epidemiologia , Filogenia , Células Vero , Vírus da Influenza A Subtipo H7N3 , Camundongos Endogâmicos C57BL , Animais Selvagens , Patos , Mamíferos
12.
Neurourol Urodyn ; 43(6): 1311-1320, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38149784

RESUMO

BACKGROUND: Bladder diaries represent a fundamental component in the assessment of patients presenting with lower urinary tract symptoms. Nevertheless, their importance often remains underappreciated and undervalued within clinical practice. This paper aims to conduct a comprehensive review of the existing literature concerning the utility of bladder diaries, underscore the criticality of their precision, elucidate the factors contributing to noncompliance with bladder diary completion, and investigate potential strategies for enhancing patient compliance. MATERIALS AND METHODS: A review of the English-language scientific literature available in the domains of Medline, Embase, Emcare, Midirs, and Cinahl was conducted. This was supplemented by discussion at the International Consultation on Incontinence Research Society Proposal session to define knowledge and identify gaps in knowledge surrounding the utility of bladder diaries. The existing evidence and outcome of the relevant discussion held in the meeting are presented. RESULTS: Bladder diaries (BD) serve to characterize the nature and severity of storage lower urinary tract symptoms (LUTS) and provide an objective record of an individual's urination patterns. They aid in the refinement and customization of treatment strategies based on the clinical responses documented in the diary, optimizing treatment outcomes. Notably, both BD and urodynamic studies (UDS) play complementary yet distinct roles in LUTS evaluation. BD offers a more comprehensive and accessible approach to assessing specific storage LUTS, particularly due to their affordability and widespread availability, especially in resource-limited settings. Nevertheless, the absence of a standardized BD format across global healthcare systems presents a significant challenge. Despite being recognized as reliable, noninvasive, validated, and cost-effective tools for evaluating patients with LUTS, the implementation and completion of BD have proven to be complex. The introduction of automated bladder diaries heralds an era of precise, real-time data collection, potentially enhancing the patient-clinician relationship. Completion of bladder diaries depends on an array of individual, social, and healthcare-specific factors. Compliance with bladder diary completion could be enhanced with clear instructions, patient education, regular follow-ups and positive re-enforcement. This study has identified four critical areas for future research: Addressing healthcare disparities between affluent and developing nations, enhancing the current functionality and effectiveness of bladder diaries, exploring the feasibility of incorporating bladder diaries into the treatment and education process and improving the quality and functionality of existing bladder diaries. CONCLUSION: Bladder diaries play a pivotal role in the evaluation and management of patients with LUTS, providing a holistic perspective. When their complete potential is harnessed, they have the capacity to revolutionize the paradigm of LUTS management, ushering in a patient-centered era of care.


Assuntos
Sintomas do Trato Urinário Inferior , Bexiga Urinária , Humanos , Sintomas do Trato Urinário Inferior/fisiopatologia , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/terapia , Bexiga Urinária/fisiopatologia , Cooperação do Paciente , Incontinência Urinária/terapia , Incontinência Urinária/diagnóstico , Incontinência Urinária/fisiopatologia , Diários como Assunto , Prontuários Médicos , Urodinâmica , Micção/fisiologia
13.
Neurourol Urodyn ; 43(6): 1321-1327, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38289324

RESUMO

AIMS: This International Consultation on Incontinence-Research Society report aims to summarize the evidence and uncertainties regarding the use of hormone replacement therapy by any route in the management of lower urinary tract symptoms (LUTS) including recurrent urinary tract infections (rUTI), with a review of special considerations for the elderly. Research question proposals to further this field have been highlighted. METHODS: An overview of the existing evidence, guidelines, and consensus regarding the use of topical or systemic estrogens in the management of LUTS. RESULTS: There are currently evidence and recommendations to offer topical estrogens to postmenopausal women with overactive bladder symptoms as well as postmenopausal women with rUTIs. Systemic estrogens however have been shown in a meta-analysis to have a negative effect on LUTS and, therefore are not currently recommended. CONCLUSIONS: Although available evidence and recommendations exist for the use of topical estrogens, few women are commenced on these in primary care. There remain large gaps still within our knowledge of the use of estrogens within the management of LUTS, particularly on when it should be commenced, the length of time treatment should be continued for, and barriers to prescribing.


Assuntos
Terapia de Reposição de Estrogênios , Sintomas do Trato Urinário Inferior , Pós-Menopausa , Humanos , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/fisiopatologia , Feminino , Estrogênios/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/diagnóstico
14.
J Biochem Mol Toxicol ; 38(8): e23799, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39132768

RESUMO

It is well established that pyruvate kinase M2 (PKM2) activity contributes to metabolic reprogramming in various cancers, including colorectal cancer (CRC). Estrogen or 17ß-estradiol (E2) signaling is also known to modulate glycolysis markers in cancer cells. However, whether the inhibition of PKM2 combined with E2 treatment could adversely affect glucose metabolism in CRC cells remains to be investigated. First, we confirmed the metabolic plasticity of CRC cells under varying environmental conditions. Next, we identified glycolysis markers that were upregulated in CRC patients and assessed in vitro mRNA levels following E2 treatment. We found that PKM2 expression, which is highly upregulated in CRC clinical samples, is not altered by E2 treatment in CRC cells. In this study, glucose uptake, generation of reactive oxygen species (ROS), lactate production, cell viability, and apoptosis were evaluated in CRC cells following E2 treatment, PKM2 silencing, or a combination of both. Compared to individual treatments, combination therapy resulted in a significant reduction in cell viability and enhanced apoptosis. Glucose uptake and ROS production were markedly reduced in PKM2-silenced E2-treated cells. The data presented here suggest that E2 signaling combined with PKM2 inhibition cumulatively targets glucose metabolism in a manner that negatively impacts CRC cell growth. These findings hold promise for novel therapeutic strategies targeting altered metabolic pathways in CRC.


Assuntos
Neoplasias Colorretais , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Hormônios Tireóideos/metabolismo , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Estrogênios/farmacologia , Proteínas de Ligação a Hormônio da Tireoide , Estradiol/farmacologia , Apoptose/efeitos dos fármacos , Glucose/metabolismo , Proteínas de Transporte/metabolismo , Piruvato Quinase/metabolismo , Piruvato Quinase/antagonistas & inibidores , Piruvato Quinase/genética , Glicólise/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Feminino
15.
BMC Cardiovasc Disord ; 24(1): 362, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014315

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been presented as a potential therapeutic option for patients with cardiogenic shock complicating myocardial infarction (CS-MI). We aimed to investigate the efficacy and safety of ECMO in CS-MI. METHODS: A systematic review and meta-analysis synthesizing evidence from randomized controlled trials obtained from PubMed, Embase, Cochrane, Scopus, and Web of Science until September 2023. We used the random-effects model to report dichotomous outcomes using risk ratio and continuous outcomes using mean difference with a 95% confidence interval. Finally, we implemented a trial sequential analysis to evaluate the reliability of our results. RESULTS: We included four trials with 611 patients. No significant difference was observed between ECMO and standard care groups in 30-day mortality with pooled RR of 0.96 (95% CI: 0.81-1.13, p = 0.60), acute kidney injury (RR: 0.65, 95% CI: 0.41-1.03, p = 0.07), stroke (RR: 1.16, 95% CI: 0.38-3.57, p = 0.80), sepsis (RR: 1.06, 95% CI: 0.77-1.47, p = 0.71), pneumonia (RR: 0.99, 95% CI: 0.58-1.68, p = 0.96), and 30-day reinfarction (RR: 0.95, 95% CI: 0.25-3.60, p = 0.94). However, the ECMO group had higher bleeding events (RR: 2.07, 95% CI: 1.44-2.97, p < 0.0001). CONCLUSION: ECMO did not improve clinical outcomes compared to the standard of care in patients with CS-MI but increased the bleeding risk.


Assuntos
Oxigenação por Membrana Extracorpórea , Infarto do Miocárdio , Ensaios Clínicos Controlados Aleatórios como Assunto , Choque Cardiogênico , Humanos , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Choque Cardiogênico/terapia , Choque Cardiogênico/mortalidade , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/etiologia , Choque Cardiogênico/fisiopatologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Infarto do Miocárdio/diagnóstico , Resultado do Tratamento , Fatores de Risco , Masculino , Feminino , Pessoa de Meia-Idade , Medição de Risco , Idoso , Fatores de Tempo
16.
BMC Vet Res ; 20(1): 74, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402395

RESUMO

BACKGROUND: Regional anesthesia is the favored choice in ruminant animals compared to general anesthesia, primarily due to its high safety margin and reduced demand for cost-intensive equipment in addition to its field applicability. Ultrasound-guided nerve block has gained significant attention in the field of veterinary medicine. This study utilized twenty-seven sheep of the native Rahmani breed to both demonstrate and evaluate the effectiveness of the ultrasound guided inferior alveolar nerve block technique. METHODS: The research comprised three phases: Phase 1 involved an anatomical examination of mandibles and sheep heads to locate the mandibular foramen and delineate the mandibular nerve course. Phase 2 included ultrasound-guided injection of methylene blue dye at specific sites along the mandibular nerve in cadaveric sheep heads. In Phase 3, clinical implementation of ultrasound-guided inferior alveolar nerve blocks was conducted in 27 live sheep, assessing efficacy, onset, and duration. RESULTS: Vertical extraoral ultrasound-guided nerve block was achieved successfully in 25 sheep (98%). A preliminary cadaveric study showed good distribution of the injectate at the mandibular nerve site. The mean onset time was 138 ± 18 s, and the mean duration time was 54 ± 4.1 min. Prominent analgesia of the ipsilateral mandible, medial surface of the cheek, and lateral border of the tongue was observed. CONCLUSIONS: Ultrasound-guided mandibular nerve block holds promise as a technique for providing effective and safe anesthesia in sheep undergoing mandibular procedures.


Assuntos
Bloqueio Nervoso , Doenças dos Ovinos , Animais , Cadáver , Nervo Mandibular , Bloqueio Nervoso/veterinária , Ovinos/cirurgia , Ultrassonografia , Ultrassonografia de Intervenção/veterinária
17.
BMC Psychiatry ; 24(1): 78, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38281929

RESUMO

BACKGROUND AND AIM: Emergence agitation (EA) after general anesthesia is common in patients with post-traumatic stress disorder (PTSD). Due to the recent worldwide events such as the Covid-19 pandemic and wars, PTSD is not rare. Accordingly, a reliable, cost-effective anesthetic protocol to lower the incidence of EA is crucial. Therefore, we aimed to compare three different interventions for avoiding EA in PTSD patients undergoing gynecological laparoscopic surgery. Participants were divided into four groups: 1: performing pre-operative relaxation techniques (deep breathing exercise and progressive muscle relaxation [PMR]); 2: administrating intra-operative Ketamine; 3: applying both previously mentioned strategies and 4 as controls. METHODS: This study was carried out on 144 adult women scheduled for gynecological laparoscopy, randomly allocated into four groups: three intervention groups and a control group (36 each). Women aged 18-45 years old, with a diagnosis of PTSD were included in the study. Patients with a positive history of major neurological, cardiovascular, metabolic, respiratory, or renal disease were excluded. Any patient who reported the use of psychiatric drugs were also excluded from the study. Data was analyzed using IBM SPSS Statistics software version 26. Kolmogorov- Smirnov was used to verify the normality of the distribution of variables. Odds ratio was calculated to clarify the strength and direction of the association between intervention groups and control. Data was deemed significant at a p-value ≤0.05. RESULTS: Heart rate (HR) and Mean Arterial Blood Pressure (MABP) intra-operative and post-operative till 24 hours were significantly lower in groups 1, 2, and 3 compared to group 4 (p<0.001). There was a significant statistical difference in the intraoperative HR percentage decrease. MABP percentage decrease post-operative was higher in all the intervention groups with no statistically significant difference, except for group 1 compared to group 4, which was statistically significant (12.28 ± 11.77 and 6.10 ± 7.24, p=0.025). Visual Analogue Scale measurements were significantly less in the intervention groups 1, 2, and 3 compared to group 4. On Riker sedation-agitation scores, group 1 was 85 times more likely to be non-agitated (85 (15.938 - 453.307), p<0.001), group 2 was 175 times more likely to be non-agitated (175 (19.932-1536.448), p<0.001) and group 3 was protected against agitation. CONCLUSION: Pre-operative relaxation techniques (breathing exercises and PMR) significantly lowered HR, MABP, VAS score, and EA than controls. These effects were not significantly different from intra-operative ketamine injection or the combination of both (relaxation techniques and ketamine). We recommend routine pre-operative screening for PTSD and the application of relaxation techniques (breathing exercises and PMR) in the pre-operative preparation protocol of PTSD-positive cases as well as routine practical application of preoperative relaxation techniques. Further studies on using pre-operative relaxation techniques in general could be cost-effective.


Assuntos
Delírio do Despertar , Ketamina , Laparoscopia , Transtornos de Estresse Pós-Traumáticos , Adulto , Humanos , Feminino , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Delírio do Despertar/etiologia , Delírio do Despertar/prevenção & controle , Transtornos de Estresse Pós-Traumáticos/etiologia , Pandemias
18.
Eur J Pediatr ; 183(8): 3263-3275, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38703279

RESUMO

The aim of this study is to study cardio-respiratory effects of nasal high-frequency oscillatory ventilation (NHFOV) vs. NCPAP as an initial mode of ventilation in moderate-late-preterm infants. A randomized controlled trial was conducted in NICU of Alexandria University Maternity Hospital (AUMH). One-hundred late-moderate-preterm infants were randomly assigned to either NHFOV-group (n = 50) or NCPAP-group (n = 50). For both groups, functional echocardiography was performed in the first 24 h to detect hemodynamic changes and respiratory outcome was monitored throughout the hospital stay. The main outcomes were hemodynamic measurements and myocardial function using functional echocardiography of those infants along with the respiratory outcome and complications. Kaplan-Meier survival plot was used representing time course of NCPAP and NHFOV failure. Left ventricular output values were not significantly different in both groups with median 202 ml/kg /min and IQR (176-275) in NCPAP-group and 226 ml/kg/min with IQR (181-286) in NHFOV group. Nevertheless, ejection fraction and fractional shortening were significantly higher in NHFOV-group with P 0.001. The time to weaning, the time to reach 30%-FIO2, the need for invasive ventilation, oxygen support duration, and maximal-FIO2 were significantly more in NCAPAP group.     Conclusion: NHFOV is an effective and promising tool of non-invasive-ventilation which can be used as a primary modality of respiratory support in preterm infants with variable forms of respiratory distress syndrome without causing detrimental effect on hemodynamics or significant respiratory complications.     Trial registration: NCT05706428 (registered on January 21, 2023). What is Known: • NHFOV might be beneficial as a secondary mode of ventilation and might have an impact on hemodynamics. What is New: • NHFOV can be used as an initial mode of ventilation with CDP beyond the reported pressure limits of CPAP without causing neither CO2 retention nor adverse hemodynamic consequences.


Assuntos
Hemodinâmica , Ventilação de Alta Frequência , Recém-Nascido Prematuro , Humanos , Recém-Nascido , Feminino , Masculino , Hemodinâmica/fisiologia , Ventilação de Alta Frequência/métodos , Ecocardiografia , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Síndrome do Desconforto Respiratório do Recém-Nascido/fisiopatologia , Resultado do Tratamento
19.
Palliat Med ; 38(5): 555-571, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38600058

RESUMO

BACKGROUND: Telephone advice lines have been recommended internationally to support around-the-clock care for people living at home with advanced illness. While they undoubtedly support care, there is little evidence about what elements are needed for success. A national picture is needed to understand, improve and standardise service delivery/care. AIM: To explore telephone advice lines for people living at home with advanced illness across the four UK nations, and to construct a practical framework to improve services. DESIGN: A cross-national evaluation of telephone advice lines using structured qualitative interviews. A patient and public involvement workshop was conducted to refine the framework. SETTING/PARTICIPANTS: Professionals with responsibilities for how palliative care services are delivered and/or funded at a local or regional level, were purposively sampled. RESULTS: Seventy-one interviews were conducted, covering 60 geographical areas. Five themes were identified. Availability: Ten advice line models were described. Variation led to confusion about who to call and when. Accessibility, awareness and promotion: It was assumed that patients/carers know who to call out-of-hours, but often they did not. Practicalities: Call handlers skills/expertise varied, which influenced how calls were managed. Possible responses ranged from signposting to organising home visits. Integration/continuity of care: Integration between care providers was limited by electronic medical records access/information sharing. Service structure/commissioning: Sustained funding was often an issue for charitably funded organisations. CONCLUSIONS: Our novel evidence-based practical framework could be transformative for service design/delivery, as it presents key considerations relating to the various elements of advice lines that may impact on the patient/carer experience.


Assuntos
Cuidadores , Cuidados Paliativos , Pesquisa Qualitativa , Humanos , Cuidadores/psicologia , Reino Unido , Adulto , Serviços de Assistência Domiciliar , Feminino , Linhas Diretas , Masculino , Telefone
20.
BMC Pregnancy Childbirth ; 24(1): 332, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724919

RESUMO

BACKGROUND: Anemia remains a major global public health issue, affecting around 24.8% of the world's population in both developing and developed countries. Pregnant women in developing countries are particularly susceptible, with 38.2% affected worldwide. Anemia is also a major contributor to maternal mortality, with 510,000 maternal deaths globally, of which 20% occur in developing countries and are related to anemia. Iron deficiency anemia is the most prevalent form, impacting 1.3 to 2.2 billion individuals, with 50% being women of reproductive age. AIM: This study aimed to assess the prevalence and associated factors of anemia in pregnant women attending antenatal care (ANC) at Hargeisa Group Hospital (HGH), Somaliland. METHODS: A cross-sectional study included 360 pregnant women, who sought ANC at HGH from July 15 to August 6, 2023. The study subjects were selected using systematic random sampling. Data were collected through structured questionnaires and participants' current medical charts, including hemoglobin levels. Data analysis was performed using SPSS software (version 20). RESULTS: The study revealed an overall prevalence of anemia among pregnant women at 50.6% (95% CI: 45.40 - 55.72%). Anemia severity was categorized as mild (33.0%), moderate (54.9%), and severe (12.1%). Factors statistically associated with anemia included gestational age in the third trimester (AOR = 3.248, 95% CI: 1.491-7.074), lack of ANC visits (AOR = 6.828, 95% CI: 1.966-23.721), and absence of iron supplementation (AOR = 29.588, 95% CI: 2.922-299.713). Notably, a higher consumption of meat per week was associated with a reduced risk of anemia (AOR = 0.198, 95% CI: 0.104-0.379). CONCLUSION: The study underscores the severity of anemia in pregnant women within the range considered as severe public health problem by WHO. It is crucial to emphasize effective prenatal care, improve dietary practices, and promote the provision of iron supplements. Enhanced maternal education on Anemia during ANC visits has the potential to reduce Anemia prevalence and mitigate adverse maternal and neonatal outcomes.


Assuntos
Anemia , Complicações Hematológicas na Gravidez , Cuidado Pré-Natal , Humanos , Feminino , Gravidez , Prevalência , Estudos Transversais , Adulto , Anemia/epidemiologia , Cuidado Pré-Natal/estatística & dados numéricos , Complicações Hematológicas na Gravidez/epidemiologia , Adulto Jovem , Fatores de Risco , Somália/epidemiologia , Anemia Ferropriva/epidemiologia
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