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BACKGROUND: Risk stratification for patients undergoing coronary artery bypass surgery (CABG) for left main coronary artery (LMCA) disease is essential for informed decision-making. This study explored the potential of machine learning (ML) methods to identify key risk factors associated with mortality in this patient group. METHODS: This retrospective cohort study was conducted on 866 patients from the Gulf Left Main Registry who presented between 2015 and 2019. The study outcome was hospital all-cause mortality. Various machine learning models [logistic regression, random forest (RF), k-nearest neighbor, support vector machine, naïve Bayes, multilayer perception, boosting] were used to predict mortality, and their performance was measured using accuracy, precision, recall, F1 score, and area under the receiver operator characteristic curve (AUC). RESULTS: Nonsurvivors had significantly greater EuroSCORE II values (1.84 (10.08-3.67) vs. 4.75 (2.54-9.53) %, P<0.001 for survivors and nonsurvivors, respectively). The EuroSCORE II score significantly predicted hospital mortality (OR: 1.13 (95% confidence interval: 1.09-1.18), P<0.001), with an AUC of 0.736. RF achieved the best ML performance (accuracy=98, precision=100, recall=97 and F1 score=98). Explainable artificial intelligence using SHAP demonstrated the most important features as follows: preoperative lactate level, emergency surgery, chronic kidney disease (CKD), NSTEMI, nonsmoking status, and sex. QLattice identified lactate and CKD as the most important factors for predicting hospital mortality this patient group. CONCLUSION: This study demonstrates the potential of ML, particularly the Random Forest, to accurately predict hospital mortality in patients undergoing CABG for LMCA disease and its superiority over traditional methods. The key risk factors identified, including preoperative lactate levels, emergency surgery, chronic kidney disease, NSTEMI, nonsmoking status, and sex, provide valuable insights for risk stratification and informed decision-making in this high-risk patient population. Additionally, incorporating newly identified risk factors into future risk scoring systems can further improve mortality prediction accuracy.
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The current study aims to evaluate the levels of miR-34a, RASSF1A, and E-cadherin in relation to the levels of isoform B of progesterone receptor (PRB) in endometrioid carcinoma (EC) and atypical hyperplasia (AEH) and their association with clinicopathological parameters. 105 cases (35 EC, 35 AEH, and 35 control) were involved in this study. Cases of AEH received treatment, and other samples were obtained after 6 months to assess the response. E-cadherin and PRB were assessed by immunohistochemistry (IHC), RASSFA methylation by MSP-PCR, and its serum level by ELISA and miR-34a via quantitative PCR. The expressions of miR-34a, RASSF1A, E-cadherin, and PRB differ among the studied groups; all were higher in normal compared with AEH and EC, with a statistically significant difference. The higher PRB expression and decreased miR-34a and RASSF1A expression were associated with resistance to hormonal therapy in AEH. High PRB in EC is associated with lower RASSFA1, E-cadherin, and miR-34a. Decreased expressions of RASSF1A, miR-34a, and E-cadherin had a significant connection to advanced stages. Expression of PRB and miR-34a and serum levels of RASSF1A predict response to treatment in cases of AEH. High PRB and low E-cadherin expression are associated with progressive disease in EC.
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BACKGROUND: The choice of prosthesis for aortic valve replacement (AVR) remains challenging. The risk of anticoagulation complications vs. the risk of aortic valve reintervention should be weighed. This study compared the outcomes of bioprosthetic vs. mechanical AVR in patients older and younger than 50. METHODS: This retrospective study was conducted from 2009 to 2019 and involved 292 adult patients who underwent isolated AVR. The patients were divided according to their age (above 50 years or 50 years and younger) and the type of valves used in each age group. The outcomes of bioprosthetic valves (Groups 1a (>50 years) and 1b (≤50 years)) were compared with those of mechanical valves (Groups 2a (>50 years) and 2b (≤50 years)) in each age group. RESULTS: The groups had nearly equal rates of preexisting comorbidities except for Group 1b, in which the rate of hypertension was greater (32.6% vs. 14.7%; p = 0.025). This group also had higher rates of old stroke (8.7% vs. 0%, p = 0.011) and higher creatinine clearance (127.62 (108.82-150.23) vs. 110.02 (84.87-144.49) mL/min; p = 0.026) than Group 1b. Patients in Group 1a were significantly older than Group 2a (64 (58-71) vs. 58 (54-67) years; p = 0.002). There was no significant difference in the NYHA class between the groups. The preoperative ejection fraction and other echocardiographic parameters did not differ significantly between the groups. Re-exploration for bleeding was more common in patients older than 50 years who underwent mechanical valve replacement (p = 0.021). There was no difference in other postoperative complications between the groups. The groups had no differences in survival, stroke, or bleeding rates. Aortic valve reintervention was significantly greater in patients ≤ 50 years old with bioprosthetic valves. There were no differences between groups in the changes in left ventricular mass, ejection fraction, or peak aortic valve pressure during the 5-year follow-up. CONCLUSIONS: The outcomes of mechanical and bioprosthetic valve replacement were comparable in patients older than 50 years. Using bioprosthetic valves in patients younger than 50 years was associated with a greater rate of valve reintervention, with no beneficial effect on the risk of bleeding or stroke.
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BACKGROUND: Adrenalectomy for pheochromocytoma (PHEO) is challenging because of the high risk of intraoperative hemodynamic instability (HDI). This study aimed to compare the incidence and risk factors of intraoperative HDI between laparoscopic left adrenalectomy (LLA) and laparoscopic right adrenalectomy (LRA). METHODS: We retrospectively analyzed two hundred and seventy-one patients aged > 18 years with unilateral benign PHEO of any size who underwent transperitoneal laparoscopic adrenalectomy at our hospitals between September 2016 and September 2023. Patients were divided into LRA (N = 122) and LLA (N = 149) groups. Univariate and multivariate logistic regression analyses were used to predict intraoperative HDI. In multivariate analysis for the prediction of HDI, right-sided PHEO, PHEO size, preoperative comorbidities, and preoperative systolic blood pressure were included. RESULTS: Intraoperative HDI was significantly higher in the LRA group than in the LLA (27% vs. 9.4%, p < 0.001). In the multivariate regression analysis, right-sided tumours showed a higher risk of intraoperative HDI (odds ratio [OR] 5.625, 95% confidence interval [CI], 1.147-27.577, p = 0.033). The tumor size (OR 11.019, 95% CI 3.996-30.38, p < 0.001), presence of preoperative comorbidities [diabetes mellitus, hypertension, and coronary heart disease] (OR 7.918, 95% CI 1.323-47.412, p = 0.023), and preoperative systolic blood pressure (OR 1.265, 95% CI 1.07-1.495, p = 0.006) were associated with a higher risk of HDI in both LRA and LLA, with no superiority of one side over the other. CONCLUSION: LRA was associated with a significantly higher intraoperative HDI than LLA. Right-sided PHEO was a risk factor for intraoperative HDI.
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Neoplasias das Glândulas Suprarrenais , Adrenalectomia , Hemodinâmica , Complicações Intraoperatórias , Laparoscopia , Feocromocitoma , Humanos , Feocromocitoma/cirurgia , Adrenalectomia/métodos , Adrenalectomia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Neoplasias das Glândulas Suprarrenais/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Fatores de Risco , IdosoRESUMO
OBJECTIVE: This scoping review aims to map the available literature and provide an overview of the published articles discussing the impact of electronic prescribing on medication errors and pharmacy workflow. METHODS: The literature search was conducted using PubMed®, Web of Science®, and the Cochrane Database of Systematic Reviews®, as well as grey literature reports, using the search terms and related components of "pharmacists", "electronic prescribing", "medication errors", and "efficiency". The search included all articles that were published from January 2011 to September 2023. Twenty-two relevant articles were identified and fully reviewed, ten of which were included in this review. RESULTS: Electronic prescribing (e-prescribing) provides a solution for some of the challenges that are associated with handwritten and paper prescriptions. However, the implementation of e-prescribing systems has been recognized as a source of new unforeseen medication errors in all the reviewed articles. Productivity in community pharmacies has been affected with receiving electronic prescriptions (e-prescriptions) and having to deal with the issues that arise from them. The pharmacists' interventions were not eliminated with e-prescriptions compared to other prescription formats. The most frequently reported reason for intervention was related to incomplete instructions in the field of directions of use. Other common challenges with e-prescriptions were related to missing information, quantity, inappropriate dose, dosage form, and drug. DISCUSSION: This review demonstrates the scarcity of research about the impact of electronic prescribing on medication error and efficiency in community pharmacies. In the literature, most of the studies had mainly focused on hospital pharmacies. The literature search demonstrated that there are still some barriers to overcome with e-prescribing systems and that medication errors were not fully eliminated with e-prescriptions. New errors have been identified with e-prescriptions, all of which caused delays in processing, which affected the productivity of the pharmacy staff, and could have negatively impacted patients' safety if not properly resolved. CONCLUSION: e-Prescribing solved some of the challenges associated with illegibility of handwritten prescriptions. However, more time is required to allow e-prescribing systems to mature. Further training for prescribers and pharmacists is also recommended before and after the implementation.
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Background: Preoperative intra-aortic balloon pump (IABP) before coronary artery bypass grafting (CABG) could improve operative outcomes by augmenting the diastolic coronary blood flow. Data on preoperative IABP use in patients with left-main coronary artery (LMCA) disease are limited. This study aimed to characterize patients who received preoperative IABP before CABG for LMCA and evaluate its effect on postoperative outcomes. Methods: This multicenter retrospective cohort study that included consecutive 914 patients who underwent CABG for unprotected LMCA disease from January 2015 to December 2019 in 14 tertiary referral centers. Patients were grouped according to the preoperative IABP insertion into patients with IABP (n=101) and without IABP (n=813). Propensity score matching adjusting for preoperative variables, with 1:1 match and a caliber of 0.03 identified 80 matched pairs. The primary outcomes used in propensity score matching were cardiac mortality and major adverse cardiac and cerebrovascular events (MACCE). Results: IABP was commonly inserted in patients with previous myocardial infarction (MI), chronic kidney disease, peripheral arterial disease, and congestive heart failure. IABP patients had higher EuroSCORE [ES >8%: 95 (11.86%) vs. 40 (39.60%), P<0.001] and SYNTAX {29 [interquartile range (IQR) 25-35] vs. 33 (IQR 26-36); P=0.02} scores. Preoperative cardiogenic shock and arrhythmia were more prevalent in patients with IABP, while acute coronary syndrome was more prevalent in patients without IABP. After matching, there was no difference in vasoactive inotropic score between groups [3.5 (IQR 1-7.5) vs. 6 (IQR 1-13.5), P=0.06], and lactate levels were nonsignificantly higher in patients with IABP [2.4 (IQR 1.4-4.5) vs. 3.1 (IQR 1.05-7.75), P=0.05]. There were no differences between groups in acute kidney injury [20 (25%) vs. 26 (32.5%), P=0.34], cerebrovascular accidents [3 (3.75%) vs. 4 (5%), P>0.99], heart failure [5 (6.25%) vs. 7 (8.75%), P=0.75], MI [7 (8.75%) vs. 8 (10%), P>0.99], major adverse cardiac and cerebrovascular events [10 (12.5%) vs. 17 (21.25%), P=0.21], and cardiac mortality [6 (7.50%) vs. 14 (17.50%), P=0.09]. Patients who received IABP had longer ventilation times [8.5 (IQR 6-23) vs. 15.5 (IQR 5-50.5) h, P=0.03] and intensive care unit (ICU) stays [3 (IQR 2-5) vs. 4 (IQR 2-7.5) days, P=0.01]. Conclusions: Preoperative IABP in patients with LMCA might not be associated with reduced cardiac mortality or hospital complications. IABP could increase the duration of mechanical ventilation and ICU stay, and its use should be individualized for each patient.
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BACKGROUND: Calcific aortic valve disease (CAVD) and mitral annular calcification (MAC) are associated with various cardiovascular diseases and may influence systemic vascular pathologies. However, their relationship with endothelial dysfunction and carotid intima-media thickness (CIMT) remains poorly elucidated. This research aims to explore the associations between MAC, aortic valve sclerosis (AVS), and markers of vascular dysfunction, specifically CIMT and endothelial function. METHODS: This prospective observational study included 200 patients undergoing routine echocardiographic evaluation at the National Heart Institute between May 2022 and April 2023. Patients were stratified into four groups namely isolated MAC (38 patients), isolated AVS (72 patients), combined MAC and AVS (50 patients), and a control group without MAC or AVS (40 patients). All participants underwent comprehensive cardiovascular evaluation, including transthoracic echocardiography (TTE) and carotid duplex ultrasonography. Endothelial function was determined by measuring reactive hyperemia-induced alterations in brachial artery diameter. RESULTS: The mean age of participants was 60.6±8.4 years, with a predominance of male subjects (64%). No significant differences were noted in baseline demographic and clinical characteristics across the groups. Patients with isolated AVS, isolated MAC, and both conditions demonstrated increased CIMT compared to controls, with significant differences noted in the combined MAC and AVS group compared to controls (p-value=0.031). Endothelial dysfunction was observed in 14.8% of the AVS group and 21.1% in the combined group, but no significant differences existed when compared to controls. The study also revealed that patients with AVS are more likely to exhibit increased CIMT (p-value=0.008). CONCLUSIONS: Both MAC and AVS are connected to increased CIMT, suggesting a link with systemic atherosclerotic processes. Although the existence of endothelial dysfunction was not significantly higher in patients with valvular calcifications, the findings support the need for further research into the cardiovascular implications of CAVD and MAC.
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Spinal cord stimulation (SCS) has emerged as a therapeutic tool for improving motor function following spinal cord injury. While many studies focus on restoring locomotion, little attention is paid to enabling standing which is a prerequisite of walking. In this study, we fully characterize a new type of response to SCS, a long extension activated post-stimulation (LEAP). LEAP is primarily directed to ankle extensors and hence has great clinical potential to assist postural movements. To characterize this new response, we used the decerebrate cat model to avoid the suppressive effects of anesthesia, and combined EMG and force measurement in the hindlimb with intracellular recordings in the lumbar spinal cord. Stimulation was delivered as five-second trains via bipolar electrodes placed on the cord surface, and multiple combinations of stimulation locations (L4 to S2), amplitudes (50-600 uA), and frequencies (10-40 Hz) were tested. While the optimum stimulation location and frequency differed slightly among animals, the stimulation amplitude was key for controlling LEAP duration and amplitude. To study the mechanism of LEAP, we performed in vivo intracellular recordings of motoneurons. In 70% of motoneurons, LEAP increased at hyperpolarized membrane potentials indicating a synaptic origin. Furthermore, spinal interneurons exhibited changes in firing during LEAP, confirming the circuit origin of this behavior. Finally, to identify the type of afferents involved in generating LEAP, we used shorter stimulation pulses (more selective for proprioceptive afferents), as well as peripheral stimulation of the sural nerve (cutaneous afferents). The data indicates that LEAP primarily relies on proprioceptive afferents and has major differences from pain or withdrawal reflexes mediated by cutaneous afferents. Our study has thus identified and characterized a novel postural motor response to SCS which has the potential to expand the applications of SCS for patients with motor disorders.
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The mitochondrial anti-viral signaling (MAVS) protein is an intermediary adaptor protein of retinoic acid-inducible gene-1 (RIG-I) like receptor (RLR) signaling, which activates the transcription factor interferon (IFN) regulatory factor 3 (IRF3) and NF-kB to produce type I IFNs. MAVS expression has been reported in different fish species, but few studies have shown its functional role in anti-viral responses to fish viruses. In this study, we used the transcription activator-like effector nuclease (TALEN) as a gene editing tool to disrupt the function of MAVS in Chinook salmon (Oncorhynchus tshawytscha) embryonic cells (CHSE) to understand its role in induction of interferon I responses to infections with the (+) RNA virus salmonid alphavirus subtype 3 (SAV-3), and the dsRNA virus infectious pancreatic necrosis virus (IPNV) infection. A MAVS-disrupted CHSE clone with a 7-aa polypeptide (GVFVSRV) deletion mutation at the N-terminal of the CARD domain infected with SAV-3 resulted in significantly lower expression of IRF3, IFNa, and ISGs and increased viral titer (1.5 log10) compared to wild-type. In contrast, the IPNV titer in MAVS-disrupted cells was not different from the wild-type. Furthermore, overexpression of salmon MAVS in MAVS-disrupted CHSE cells rescued the impaired type I IFN-mediated anti-viral effect against SAV-3.
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Proteínas Adaptadoras de Transdução de Sinal , Infecções por Alphavirus , Alphavirus , Doenças dos Peixes , Vírus da Necrose Pancreática Infecciosa , Transdução de Sinais , Replicação Viral , Animais , Vírus da Necrose Pancreática Infecciosa/fisiologia , Vírus da Necrose Pancreática Infecciosa/imunologia , Alphavirus/imunologia , Alphavirus/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Infecções por Alphavirus/imunologia , Infecções por Alphavirus/virologia , Salmão/virologia , Salmão/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/metabolismo , Fator Regulador 3 de Interferon/metabolismo , Fator Regulador 3 de Interferon/genética , Infecções por Birnaviridae/imunologia , Infecções por Birnaviridae/veterinária , Infecções por Birnaviridae/virologiaRESUMO
Tuberculosis (TB) is the world's deadliest infectious disease, with over 1.5 million deaths and 10 million new cases reported anually. The causative organism Mycobacterium tuberculosis (Mtb) can take nearly 40 d to culture, a required step to determine the pathogen's antibiotic susceptibility. Both rapid identification and rapid antibiotic susceptibility testing of Mtb are essential for effective patient treatment and combating antimicrobial resistance. Here, we demonstrate a rapid, culture-free, and antibiotic incubation-free drug susceptibility test for TB using Raman spectroscopy and machine learning. We collect few-to-single-cell Raman spectra from over 25,000 cells of the Mtb complex strain Bacillus Calmette-Guérin (BCG) resistant to one of the four mainstay anti-TB drugs, isoniazid, rifampicin, moxifloxacin, and amikacin, as well as a pan-susceptible wildtype strain. By training a neural network on this data, we classify the antibiotic resistance profile of each strain, both on dried samples and on patient sputum samples. On dried samples, we achieve >98% resistant versus susceptible classification accuracy across all five BCG strains. In patient sputum samples, we achieve ~79% average classification accuracy. We develop a feature recognition algorithm in order to verify that our machine learning model is using biologically relevant spectral features to assess the resistance profiles of our mycobacterial strains. Finally, we demonstrate how this approach can be deployed in resource-limited settings by developing a low-cost, portable Raman microscope that costs <$5,000. We show how this instrument and our machine learning model enable combined microscopy and spectroscopy for accurate few-to-single-cell drug susceptibility testing of BCG.
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Antituberculosos , Aprendizado de Máquina , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Análise Espectral Raman , Análise Espectral Raman/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana/métodos , Antituberculosos/farmacologia , Farmacorresistência Bacteriana , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Isoniazida/farmacologiaRESUMO
Regenerative dental medicine continuously expands to improve treatments for prevalent clinical problems in dental and oral medicine. Stem cell based translational opportunities include regenerative therapies for tooth restoration, root canal therapy, and inflammatory processes (e.g., periodontitis). The potential of regenerative approaches relies on the biological properties of dental stem cells. These and other multipotent somatic mesenchymal stem cell (MSC) types can in principle be applied as either autologous or allogeneic sources in dental procedures. Dental stem cells have distinct developmental origins and biological markers that determine their translational utility. Dental regenerative medicine is supported by mechanistic knowledge of the molecular pathways that regulate dental stem cell growth and differentiation. Cell fate determination and lineage progression of dental stem cells is regulated by multiple cell signaling pathways (e.g., WNTs, BMPs) and epigenetic mechanisms, including DNA modifications, histone modifications, and non-coding RNAs (e.g., miRNAs and lncRNAs). This review also considers a broad range of novel approaches in which stem cells are applied in combination with biopolymers, ceramics, and composite materials, as well as small molecules (agonistic or anti-agonistic ligands) and natural compounds. Materials that mimic the microenvironment of the stem cell niche are also presented. Promising concepts in bone and dental tissue engineering continue to drive innovation in dental and non-dental restorative procedures.
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Materiais Biocompatíveis , Medicina Regenerativa , Humanos , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Células-Tronco/citologia , Células-Tronco/metabolismo , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismo , AnimaisRESUMO
BACKGROUND: Ischemic injury is a common mechanism in both ischemic stroke (IS) and acute coronary syndrome (ACS). Matrix metalloproteinase 9 (MMP-9), an endopeptidase that degrades extracellular matrix, is important in the pathogenesis of IS. The purpose of this study is to evaluate the association between the SNP rs17576 in MMP-9 gene with (1) the risk and severity of acute ischemic stroke in Saudi Arab individuals with recent acute coronary syndrome, and (2) the risk of acute coronary syndrome in Saudi Arab individuals without ischemic stroke. METHODS: A case control study of 200 IS patients, 520 ACS patients (without IS), and 500 aged-matched healthy controls were genotyped to detect the MMP-9 polymorphism rs17156. RESULTS: Our study demonstrated a non-significant difference in the genotype and allele frequencies of the MMP9 rs17576 polymorphism between the patients with IS and patients with ACS without IS (P = 0.31 for the GA genotype, 0.25 for the AA genotype and P = 0.20 for the A allele). AA genotype was found to be statistically significant between IS and control groups; [OR=1.84, 95 % CI (1.08-3.14), p =0.015]. A allele showed a significant difference between the two groups [OR=1.28, 95 % CI (1.00-1.64), p =0.028]. By comparing ACS without IS and controls, AA genotype was significant [OR=1.46, 95 % CI (1.01-2.12), p =0.029]. Stratification by NIHSS score revealed higher mortality and early neurologic deterioration in IS patients with NIHSS score ≥ 16 (p < 0.001, 0.044 respectively). CONCLUSION: We deduced the lack of association either with allele or genotype frequencies (p>0.05) between the IS cases and the cases of ACS without IS. In contrast there was a significant association of mutant genotype AA between either the IS group or ACS (without IS) group, and the control group. In addition, different rs17576 genotypes were not associated with raised mortality or a tendency to develop early neurologic deterioration.
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Síndrome Coronariana Aguda , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , AVC Isquêmico , Metaloproteinase 9 da Matriz , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de Doença , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , AVC Isquêmico/genética , AVC Isquêmico/diagnóstico , AVC Isquêmico/mortalidade , Estudos de Casos e Controles , Metaloproteinase 9 da Matriz/genética , Idoso , Fatores de Risco , Medição de Risco , Arábia Saudita , FenótipoRESUMO
Cyclophosphamide is an anti-neoplastic drug that has shown competence in the management of a broad range of malignant tumors. In addition, it represents a keystone agent for management of immunological conditions. Despite these unique properties, induction of lung toxicity may limit its clinical use. Omarigliptin is one of the dipeptidyl peptidase-4 inhibitors that has proven efficacy in management of diabetes mellitus. Rosinidin is an anthocyanidin flavonoid that exhibited promising results in management of diseases characterized by oxidative stress, inflammation, and apoptosis. The present work investigated the possible effects of omarigliptin with or without rosinidin on cyclophosphamide-induced lung toxicity with an exploration of the molecular mechanisms that contribute to these effects. In a rodent model of cyclophosphamide elicited lung toxicity, the potential efficacy of omarigliptin with or without rosinidin was investigated at both the biochemical and the histopathological levels. Both omarigliptin and rosinidin exhibited a synergistic ability to augment the tissue antioxidant defenses, mitigate the inflammatory pathways, restore glucagon-like peptide-1 levels, modulate high mobility group box 1 (HMGB1)/receptors of advanced glycation end products (RAGE)/nuclear factor kappa B (NF-κB) axis, downregulate the fibrogenic mediators, and create a balance between the pathways involved in apoptosis and the autophagy signals in the pulmonary tissues. In conclusion, omarigliptin/rosinidin combination may be introduced as a novel therapeutic modality that attenuates the different forms of lung toxicities induced by cyclophosphamide.
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Ciclofosfamida , Peptídeo 1 Semelhante ao Glucagon , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Piranos , Transdução de Sinais , Animais , Ciclofosfamida/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Masculino , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Fosfatidilinositol 3-Quinases/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Piranos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Antocianinas/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/farmacologia , Ratos Wistar , Pirimidinas/farmacologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Proteína Forkhead Box O1 , Compostos Heterocíclicos com 2 AnéisRESUMO
The use of essential oils (EOs) has attracted interest in the food industry due to their wide range of beneficial properties. In this study, a new functional yogurt was developed using 2 essential oils [Marjoram (M) and Geranium (G)], at 3 different concentrations (0.2%, 0.4%, and 0.6% vol/vol). The physicochemical properties (syneresis, viscosity, pH, and chemical composition), bioactivities (antioxidant activity, anticancer and antibacterial effects, total phenolic content (TPC), and total flavonoid content (TFC)), and sensory characteristics of the developed yogurt were evaluated. The findings indicated that the yogurts fortified with 0.6% M or G exhibited higher viscosity and lower syneresis compared with other treatments. The yogurt supplemented with 0.6% M displayed significant antibacterial activity against Listeria monocytogenes, Staphylococcus aureus, Salmonella typhimurium, and Escherichia coli. In addition, the yogurt enriched with Geranium and Marjoram oils at a concentration of 0.6% had notably significant (P < 0.05) higher TFC levels compared with the control sample and other concentrations. In the same context, in terms of TPC, yogurt supplemented with 0.6% Marjoram oil displayed significantly (P < 0.05) elevated levels in comparison to the other samples tested. Yogurt enriched with Marjoram oil exhibited noteworthy antioxidant activity, followed by Geranium oil compared with the control samples. The yogurt supplemented with 0.6% M demonstrated strong radical scavenging activity, while the yogurt fortified with 0.6% G showed higher anticancer activity against HepG2 human liver carcinoma cells and oxidative stress enzyme activities. Among the various concentrations of EOs tested, the yogurts fortified with 0.6% M or G EOs exhibited the most favorable outcomes, followed by 0.4% M or G. To summarize, G and M EOs can be used as a potential nutritious ingredient and as a natural preservative for milk and related products.
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Background: Soft tissue defects in the lower third of the leg present significant challenges for surgeons. Despite various options available for soft tissue coverage, selecting the most suitable option is limited by potential complications. In response to this challenge, some surgeons have sought to develop algorithms to guide decision-making in the management of lower leg trauma. Methods: This prospective observational cross-sectional study included 53 patients with traumatic injuries to the lower third leg and ankle regions. Each patient underwent a management plan based on our proposed algorithm, which incorporated the utilization of negative pressure wound therapy and dermal substitutes. Outcomes were assessed in terms of the ability to achieve complete coverage, complication rates, duration of hospital stay, and return to normal daily activity. Results: The proposed algorithm proved to be comprehensive and easily applicable, achieving complete coverage in 98.1% of cases. The mean duration for definitive coverage was 21.89â ±â 12.84 days, and the majority of cases (81.1%) returned to normal daily activity within a mean duration of 60.69â ±â 56.7 days. The use of dermal substitutes resulted in achieving coverage in wounds with exposed structures, with favorable outcomes in cases with a mean size of 11.39â ±â 10.05 cm². Conclusions: Our algorithm provides a safe and effective approach to manage traumatic defects of the lower third leg and ankle, considering the patient's general condition and the complexity of the wound. Proper utilization of dermal substitutes and negative pressure wound therapy is emphasized in the algorithm.
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Natural products have a long history of success in treating bacterial infections, making them a promising source for novel antibacterial medications. Curcumin, an essential component of turmeric, has shown potential in treating bacterial infections and in this study, we covalently immobilized curcumin (Cur) onto chitosan (CS) using glutaraldehyde and tannic acid (TA), resulting in the fabrication of novel biocomposites with varying CS/Cur/TA ratios. Comprehensive characterization of these ternary biocomposites was conducted using FTIR, SEM, XPS, and XRD to assess their morphology, functional groups, and chemical structures. The inhibitory efficacy of these novel biocomposites (n = 4) against the growth and viability of Pseudomonas aeruginosa (ATCC27853) and Chromobacterium violaceum (ATCC12472) was evaluated and the most promising composite (C3) was investigated for its impact on quorum sensing (QS) and biofilm formation in these bacteria. Remarkably, this biocomposite significantly disrupted QS circuits and effectively curtailed biofilm formation in the tested pathogens without inducing appreciable toxicity. These findings underscore its potential for future in vivo studies, positioning it as a promising candidate for the development of biofilm disrupting antibacterial agents.
Assuntos
Antibacterianos , Biofilmes , Quitosana , Curcumina , Pseudomonas aeruginosa , Percepção de Quorum , Taninos , Quitosana/química , Quitosana/farmacologia , Percepção de Quorum/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Curcumina/farmacologia , Curcumina/química , Taninos/química , Taninos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Chromobacterium/efeitos dos fármacos , Testes de Sensibilidade Microbiana , PolifenóisRESUMO
Ten novel spectrophotometric approaches were developed for the initial examination of the Hydroxychloroquine and Paracetamol medications. These procedures are straightforward, specific, easy to use, and provide exact and accurate results. The determination was conducted through the utilization of several approaches, including zero order (dual wavelength, zero crossing, advanced absorption subtraction and spectrum subtraction), derivative (first derivative of zero crossing), ratio (ratio difference, ratio derivative) and mathematical (bivariate, simultaneous equation, and Q-absorbance) techniques. After undergoing validation in accordance with ICH criteria, it was established that each of these methods achieved acceptable levels of precision, repeatability, robustness, and accuracy. The advantages and disadvantages of each method are demonstrated, and the proposed and reported methodologies were statistically compared.
RESUMO
PURPOSE: We aimed to report the early results of performing acute ankle arthrodesis using a modified retrograde femoral intramedullary locking IMN concomitant with plating at the same setting for managing diabetic patients' acute ankle fractures. METHODS: We prospectively included patients who presented acutely with ankle fractures, where hemoglobin A1C (HbA1C) on admission was > 7%, and the Adelaide Fracture in the Diabetic Ankle (AFDA) algorithm score was 5 or above. All patients were treated by acute ankle arthrodesis using a modified retrograde femoral IMN combined with lateral plating. Functional assessment was reported according to a modified American Orthopaedic Foot and Ankle Society ankle hindfoot scale (AOFAS), and complications were documented. RESULTS: Six patients had an average age of 55.7 years (37-65). The average HbA1C on admission was 7.9 (7.3-9), and the average AFDA score was 7.3 (6-8). The average operative time was 79.2 min (70-90). All patients, except for one, achieved union at the arthrodesis site after an average of 10.3 weeks (8-14). After an average last follow-up of 9 months (6-12), the average modified AOFAS was 73.2 (82 to 62); four patients had an excellent score and one good. Complications developed in two, one deep infection after 2 weeks treated by metal removal and Ilizarov, and the other patient developed a stress fracture at the tibial end of the nail, which was treated by open reduction and internal fixation using a plate and screws. CONCLUSION: Using a modified femoral IMN combined with lateral plating is a promising technique to achieve ankle arthrodesis in diabetic patients with acute ankle fractures with acceptable outcomes; however, further studies with larger numbers are needed. LEVEL OF EVIDENCE: IV.