RESUMO

Herein, novel nanocomposites based on reduced graphene oxide decorated copper oxide nanoparticles (rGO/CuO) were prepared by the in situ co-precipitation method. The structural, morphological, and optical characterization of as-prepared nanocomposites was performed by powdered x-ray diffraction (p-XRD), scanning electron microscopy (SEM), and Fourier-transform infrared (FTIR), Raman, and ultraviolet-visible (UV-Vis) spectroscopy, respectively. The as-prepared nanocomposites exhibited better photocatalytic activity of rhodamine B dye with maximum ~94% degradation in 120 min with a rate constant of 0.2353 min-1 under optimized conditions. Furthermore, the effects of solution pH and catalyst loading are studied on the degradation process. Therefore, this state-of-the-art strategy for the decoration of CuO nanoparticles onto the surface of rGO nanosheets could be an ideal platform for fabricating highly efficient photocatalysts.

RESUMO

Background: Simulation is increasingly being adopted by healthcare educators throughout the developed world as it offers a safe environment to practice skills. While there is literature on learning via simulation in healthcare in the developed world, more studies are required to investigate the factors influencing this approach in the developing world. Objective: This scoping review highlights the key factors that act as deterrents as well as encouragement to the uptake of simulation as a teaching methodology in healthcare education in developing countries. Design: The MEDLINE (via OVID, using keywords and MeSH in OVID), and PubMed (via NCBI using MeSH), and CINAHL databases were searched between January 2000 and January 2024 for research articles published in peer reviewed English language journals using a combination of keywords. Results: A total of 48 articles were included in the final analysis. Challenges and opportunities were divided into professional, academic, and resource-based factors, and their individual sub-themes. The main challenges reported were the lack of a contextual curriculum, content heavy curricula, dearth of trained simulationists and cost of simulators. Performance anxiety was an important challenge reported by both trainers and trainees. Main opportunities were an interest in adopting simulation-based education from both trainers and trainees, and the opportunity to improve patient safety and quality of education. Other findings were that academic leadership and faculty show interest and urgency to adopt simulation in curricula and allocate funds for this. Facilitators need to be provided with protected time to become simulationists. Local manufacturers need to be sourced for simulators, and transfer of technology and expertise needs to be negotiated. Conclusion: Simulation needs to be looked at from the lens of not only education, but more importantly of patient safety in developing countries to allow simulation-based education to be mainstreamed in health professions education in low- and middle-income contexts.

RESUMO

OBJECTIVE: This study aimed to evaluate the accuracy and reproducibility of information provided by ChatGPT, in response to frequently asked questions (FAQs) about radiofrequency ablation (RFA) for varicose veins. METHODS: This cross-sectional study was conducted at The Aga Khan University Hospital, Karachi, Pakistan. A set of 18 FAQs regarding RFA for varicose veins were compiled from credible online sources and presented to ChatGPT twice, separately, using the 'new chat' option. Twelve experienced vascular surgeons (with over 2 years of experience and at least 20 RFA procedures performed annually) independently evaluated the accuracy of the responses using a 4-point Likert scale and assessed their reproducibility. RESULTS: Most evaluators were males (n=10/12, 83.3%) with an average of 12.3 ± 6.2 years of experience as a vascular surgeon. Six (50%) evaluators were from the UK followed by three (25.0%) from Saudi Arabia, two (16.7%) from Pakistan, and one (8.3%) from the USA. Among the 216 accuracy grades, most of the evaluators graded the responses as 'comprehensive' (n=87/216, 40.3%) or 'accurate but insufficient' (n=70/216, 32.4%), whereas only 17.1% (n=37/216) were graded as 'a mixture of both accurate and inaccurate information' and 10.8% (n=22/216) as 'entirely inaccurate'. Overall, 89.8% (n=194/216) of the responses were deemed reproducible. Of the total responses, 70.4% (n=152/216) were classified as 'good quality' and 'reproducible'. The remaining responses were 'poor quality' with 19.4% (n=42/216) 'reproducible' and 10.2% (n=22/216) 'non-reproducible'. There was non-significant inter-rater disagreement among the vascular surgeons for overall responses (Fleiss' Kappa: -0.028, p=0.131). CONCLUSION: ChatGPT provided generally accurate and reproducible information on RFA for varicose veins, however, variability in response quality and limited inter-rater reliability highlight the need for further improvements. While it has the potential to enhance patient education and support healthcare decision-making, improvements in its training, validation, transparency, and mechanisms to address inaccurate or incomplete information are essential.

RESUMO

This systematic review and meta-analysis aimed to assess the association of neutrophil-to-lymphocyte ratio (NLR) with an elevated risk of vascular access failure in end-stage renal disease (ESRD) patients undergoing hemodialysis. A comprehensive database search of MEDLINE (via PubMed), Scopus, and Cochrane Central was performed. Studies reporting the values of NLR in both functional and non-functional AVF groups in ESRD patients were selected. Quality assessment was performed using the Modified Newcastle-Ottawa scale for observational studies. Meta-analysis was performed using an inverse variance random effects model. Seven observational studies met the inclusion criteria, including 1313 participants with 554 cases and 759 controls. Pooled results showed significantly high NLR levels in patients with non-functional arteriovenous fistula (AVF) compared to functional AVF (SMD = 1.19, 95% CI = 0.74-1.65, p < 0.001). Subgroup analysis confirmed the consistency of the association between NLR and AVF failure across study design (SMD = 1.76, 95% CI = 0.78-2.73, p = 0.0004 in prospective vs SMD = 0.87, 95% CI = 0.42-1.32, p = 0.0001 in retrospective studies), etiology (SMD = 1.63, 95% CI = 0.75-2.52, p = 0.0003 in stenosis or thrombosis; and SMD = 0.80, 95% CI = 0.27-1.34, p = 0.003 in failure to mature of AVF), and NLR measurement timing (SMD = 0.98, 95% CI = 0.42-1.54, p = 0.0006 in preoperative vs SMD = 1.58, 95% CI = 0.47-2.69, p = 0.005 in postoperative NLR). The pooled odds ratio revealed high NLR values as a significant predictor of AVF failure in ESRD patients (OR = 3.91, 95% CI = 1.91-7.98, p = 0.0002). The pooled sensitivity and specificity were 89.72% (95% CI = 77.51%-95.67%) and 72.95% (95% CI = 63.82%-80.47%), respectively. The high NLR is a useful and predictive marker for AVF failure in hemodialysis patients. Future studies should prioritize larger cohort studies to validate and reinforce these observations.

RESUMO

Hydrogen production via cost-effective electrochemical water splitting is one of the most promising approaches to confront the energy crisis and to obtain clean fuels with high energy density. To address this concern, herein, we developed a simple one-step synthesis method for creating an AuAgCu trimetallic alloy using aspirin as a capping agent. This alloy shows potential for efficient electrocatalyst for hydrogen evolution reaction. The trimetallic nanoparticles based alloy exhibit an equiaxed grain-like morphology and a face-centred cubic phase. In HER experiments using a 1 M KOH electrolyte, the AuAgCu alloy shows nearly negligible overpotential compared to mono- and bimetallic catalysts, and the Tafel slope was 32.7 mV dec-1, which is the lowest ever achieved for alloy-based electrocatalysts and extremely close to a commercially available Pt/C with high stability for 21 days and no decrease in current density in alkaline media. Besides, with excellent HER activity and stability, the trimetallic AuAgCu-modified electrode possessed significant durability for over 1000 cycles in the selected range of potential from 0.5 to 0.8 V at different scan rates from 1 to 100 mV s-1. This simple, cost-effective and environmentally friendly methodology can pave the way for the exploitation of mixed metal alloy-based electrocatalysts not only for water splitting but also for other applications, such as fuel cells, lithium-ion batteries and supercapacitors.

RESUMO

Obesity is a well-known risk factor for testicular function; however, dulaglutide's effect on the testis in obesity has received little attention. Currently, clinicians prescribe the antidiabetic drug dulaglutide only off-label for weight management in non-diabetics. Investigating the impact of this novel compound on obesity is critical for determining whether it has any disruptive effects on testicular cells. We used a well-known animal model of high-fat diet-induced obesity in this investigation, and testicular dysfunction was determined by sperm DNA damage, spermatocyte chromosomal abnormalities, and spermiogram analysis. Following a 12-week high-fat diet challenge, mice were randomly assigned to dulaglutide (0.6 mg/kg/day) or saline treatments for five weeks. Testes and sperm cells were collected 24 h after the last dulaglutide injection. Untreated obese mice had a lower testes/body weight ratio, more sperm DNA damage, diakinesis-metaphase I chromosomal abnormalities, a lower sperm count/motility, more cell morphological defects, and an altered testicular redox balance. In obese mice, dulaglutide injection efficiently restored all disturbed parameters to their control levels. Dulaglutide injection into healthy mice exhibited no significant harmful effects at the applied regimen. As a result, we infer that dulaglutide therapy might bring obese men additional benefits by recovering testicular dysfunction induced by obesity.

Assuntos

Dieta Hiperlipídica , Modelos Animais de Doenças , Peptídeos Semelhantes ao Glucagon , Fragmentos Fc das Imunoglobulinas , Obesidade , Proteínas Recombinantes de Fusão , Testículo , Animais , Masculino , Fragmentos Fc das Imunoglobulinas/farmacologia , Obesidade/tratamento farmacológico , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/farmacologia , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Camundongos , Proteínas Recombinantes de Fusão/farmacologia , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Dano ao DNA/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Aberrações Cromossômicas/efeitos dos fármacos , Doenças Testiculares/tratamento farmacológico

RESUMO

The power system incorporates renewable energy resources into the main utility grid, which possesses low or no inertia, and these systems generate harmonics due to the utilization of power electronic equipment. The precise and effective assessment of harmonic characteristics is necessary for maintaining power quality in distributed power systems. In this paper, the Marine Predator Algorithm (MPA) that mimics the hunting behavior of predators is exploited for harmonics estimation. The MPA utilizes the concepts of Levy and Brownian motions to replicate the movement of predators as they search for prey. The identification model for parameter estimation of harmonics is presented, and an objective function is developed that minimizes the difference between the real and predicted harmonic signals. The efficacy of the MPA is assessed for different levels of noise, population sizes, and iterations. Further, the comparison of the MPA is conducted with a recent metaheuristic of the Reptile Search Algorithm (RSA). The statistical analyses through sufficient autonomous executions established the accurate, stable, reliable and robust behavior of MPA for all variations. The substantial enhancement in estimation accuracy indicates that MPA holds great potential as a strategy for estimating harmonic parameters in distributed power systems.

RESUMO

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is marked by impaired social interactions, and increased repetitive behaviors. There is evidence of genetic changes in ASD, and several of these altered genes are linked to the process of DNA repair. Therefore, individuals with ASD must have improved DNA repair efficiency to mitigate risks associated with ASD. Despite numerous milestones in ASD research, the disease remains incurable, with a high occurrence rate and substantial financial burdens. This motivates scientists to search for new drugs to manage the disease. Disruption of glucagon-like peptide-1 (GLP-1) signaling, a regulator in neuronal development and maintains homeostasis, has been associated with the pathogenesis and progression of several neurological disorders, such as ASD. Our study aimed to assess the impact of semaglutide, a new GLP-1 analog antidiabetic medication, on behavioral phenotypes and DNA repair efficiency in the BTBR autistic mouse model. Furthermore, we elucidated the underlying mechanism(s) responsible for the ameliorative effects of semaglutide against behavioral problems and DNA repair deficiency in BTBR mice. The current results demonstrate that repeated treatment with semaglutide efficiently decreased autism-like behaviors in BTBR mice without affecting motor performance. Semaglutide also mitigated spontaneous DNA damage and enhanced DNA repair efficiency in the BTBR mice as determined by comet assay. Moreover, administering semaglutide recovered oxidant-antioxidant balance in BTBR mice. Semaglutide restored the disrupted DNA damage/repair pathways in the BTBR mice by reducing Gadd45a expression and increasing Ogg1 and Xrcc1 expression at both the mRNA and protein levels. This suggests that semaglutide holds great potential as a novel therapeutic candidate for treating ASD traits.

Assuntos

Reparo do DNA , Peptídeos Semelhantes ao Glucagon , Animais , Masculino , Peptídeos Semelhantes ao Glucagon/farmacologia , Reparo do DNA/efeitos dos fármacos , Camundongos , Modelos Animais de Doenças , Transtorno do Espectro Autista/tratamento farmacológico , Transtorno do Espectro Autista/genética , Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Transtorno Autístico/tratamento farmacológico , Transtorno Autístico/genética , Transtorno Autístico/metabolismo , Comportamento Animal/efeitos dos fármacos

RESUMO

OBJECTIVE: To determine the frequency and pattern of different aetiologies of leg pain among patients visiting vascular surgery clinics. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Vascular Surgery Clinics of the Aga Khan University Hospital, Karachi, Pakistan, between February 2021 and June 2023. METHODOLOGY: This study examined patients presenting with leg pain for the first time at vascular surgery clinics. The socio-demographic and clinical data including the clinical symptoms, physical examination findings, and management of leg pain were noted using a specially designed proforma. RESULTS: In a total of 142 patients (200 limbs), 82 (57.7%) were females and 60 (42.3%) were males, with a mean age of 46.8 ± 15.1 years. The patients' mean body mass index (BMI) was 30.2 ± 7.9 kg/m2. Ninety-one (64.1%) patients had a predominantly standing job compared to 51 (35.9%) patients who had a predominantly sitting job. The most common aetiology of leg pain was chronic venous insufficiency (CVI), diagnosed in 107 (53.5%) patients, followed by neurogenic pain [41 (20.5%)], musculoskeletal pain including knee osteoarthritis [30 (15.0%)], and arterial insufficiency [22 (11.0%)].  Conclusion: CVI followed by neuropathic pain was the leading cause of leg pain in vascular surgery clinics at a tertiary care hospital. KEY WORDS: Chronic venous insufficiency, Arterial insufficiency, Vascular surgery, Leg pain, Musculoskeletal pain, Neuralgia.

Assuntos

Perna (Membro) , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Paquistão/epidemiologia , Adulto , Perna (Membro)/irrigação sanguínea , Procedimentos Cirúrgicos Vasculares , Dor/etiologia , Dor/epidemiologia , Neuralgia/etiologia , Neuralgia/epidemiologia , Idoso , Dor Musculoesquelética/epidemiologia , Dor Musculoesquelética/etiologia

RESUMO

Obesity is an established risk factor for numerous malignancies, although it remains uncertain whether the disease itself or weight-loss drugs are responsible for a greater predisposition to cancer. The objective of the current study was to determine the impact of dulaglutide on genetic and epigenetic DNA damage caused by obesity, which is a crucial factor in the development of cancer. Mice were administered a low-fat or high-fat diet for 12 weeks, followed by a 5-week treatment with dulaglutide. Following that, modifications of the DNA bases were examined using the comet assay. To clarify the underlying molecular mechanisms, oxidized and methylated DNA bases, changes in the redox status, levels of inflammatory cytokines, and the expression levels of some DNA repair genes were evaluated. Animals fed a high-fat diet exhibited increased body weights, elevated DNA damage, oxidation of DNA bases, and DNA hypermethylation. In addition, obese mice showed altered inflammatory responses, redox imbalances, and repair gene expressions. The findings demonstrated that dulaglutide does not exhibit genotoxicity in the investigated conditions. Following dulaglutide administration, animals fed a high-fat diet demonstrated low DNA damage, less oxidation and methylation of DNA bases, restored redox balance, and improved inflammatory responses. In addition, dulaglutide treatment restored the upregulated DNMT1, Ogg1, and p53 gene expression. Overall, dulaglutide effectively maintains DNA integrity in obese animals. It reduces oxidative DNA damage and hypermethylation by restoring redox balance, modulating inflammatory responses, and recovering altered gene expressions. These findings demonstrate dulaglutide's expediency in treating obesity and its associated complications.

Assuntos

Dano ao DNA , Metilação de DNA , Reparo do DNA , Dieta Hiperlipídica , Peptídeos Semelhantes ao Glucagon , Fragmentos Fc das Imunoglobulinas , Oxirredução , Proteínas Recombinantes de Fusão , Animais , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/farmacologia , Metilação de DNA/efeitos dos fármacos , Fragmentos Fc das Imunoglobulinas/farmacologia , Dano ao DNA/efeitos dos fármacos , Camundongos , Reparo do DNA/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Masculino , Oxirredução/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/genética , Estresse Oxidativo/efeitos dos fármacos , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Obesidade/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos C57BL

RESUMO

Drilling through shale formations can be expensive and time-consuming due to the instability of the wellbore. Further, there is a need to develop inhibitors that are environmentally friendly. Our study discovered a cost-effective solution to this problem using Gum Arabic (ArG). We evaluated the inhibition potential of an ArG clay swelling inhibitor and fluid loss controller in water-based mud (WBM) by conducting a linear swelling test, capillary suction timer test, and zeta potential, fluid loss, and rheology tests. Our results displayed a significant reduction in linear swelling of bentonite clay (Na-Ben) by up to 36.1% at a concentration of 1.0 wt. % ArG. The capillary suction timer (CST) showed that capillary suction time also increased with the increase in the concentration of ArG, which indicates the fluid-loss-controlling potential of ArG. Adding ArG to the drilling mud prominently decreased fluid loss by up to 50%. Further, ArG reduced the shear stresses of the base mud, showing its inhibition and friction-reducing effect. These findings suggest that ArG is a strong candidate for an alternate green swelling inhibitor and fluid loss controller in WBM. Introducing this new green additive could significantly reduce non-productive time and costs associated with wellbore instability while drilling. Further, a dynamic linear swelling model, based on machine learning (ML), was created to forecast the linear swelling capacity of clay samples treated with ArG. The ML model proposed demonstrates exceptional accuracy (R2 score = 0.998 on testing) in predicting the swelling properties of ArG in drilling mud.

RESUMO

Enterocolic lymphocytic phlebitis is a rare lymphocytic vasculitis afflicting the gastrointestinal veins without involving the arterial system. Lymphocytic colitis is a more common pathology described as lymphocytic inflammation of the colonic epithelium. Concurrence of both these pathologies is extremely rare. We describe a 53-year-old man presenting with chronic watery diarrhea, abdominal pain, and weight loss. Colonoscopic examination revealed normal-appearing mucosa, but biopsy findings revealed lymphocytic colitis with coexisting enterocolic lymphocytic phlebitis. The patient was started on oral budesonide and responded to the treatment with symptomatic and histopathological resolution.

RESUMO

Psoriasis is classified as an autoimmune disorder characterized by abnormal immune response leading to the development of chronic dermal inflammation. Most individuals have a genetic vulnerability that may be further influenced by epigenetic changes occurring due to multiple variables such as pollutant exposure. Epigenetic modifications such as DNA methylation possess a dynamic nature, enabling cellular differentiation and adaptation by controlling gene expression. Di(2-ethylhexyl) phthalate (DEHP) and psoriatic inflammation are known to cause modification of DNA methylation via DNA methyltransferase (DNMT). However, it is not known whether DEHP, a ubiquitous plasticizer affects psoriatic inflammation via DNMT modulation. Therefore, this study investigated the effect of DNMT inhibitor, 5-aza-2'-deoxycytidine (AZA) on DEHP-induced changes in the expression of DNMT1, global DNA methylation, and anti-/inflammatory parameters (p-STAT3, IL-17A, IL-6, iNOS, IL-10, Foxp3, Nrf2, HO-1) in the skin and the peripheral adaptive/ myeloid immune cells (CD4+ T cells/CD11b+ cells) in imiquimod (IMQ) model of psoriasiform inflammation. Further, psoriasis-associated clinical/histopathological features (ear thickness, ear weight, ear PASI score, MPO activity, and H&E staining of the ear and the back skin) were also analyzed in IMQ model. Our data show that IMQ-treated mice with DEHP exposure had increased DNMT1 expression and DNA methylation which was associated with elevated inflammatory (p-STAT3, IL-17A, IL-6, iNOS) and downregulated anti-inflammatory mediators (IL-10, Foxp3, Nrf2, HO-1) in the peripheral immune cells (CD4+ T cells/CD11b+ cells) and the skin as compared to IMQ-treated mice. Treatment with DNMT1 inhibitor caused reduction in inflammatory and elevation in anti-inflammatory parameters with significant improvement in clinical/histopathological symptoms in both IMQ-treated and DEHP-exposed IMQ-treated mice. In conclusion, our study shows strong evidence indicating that DNMT1 plays an important role in DEHP-induced exacerbation of psoriasiform inflammation in mice through hypermethylation of DNA.

Assuntos

DNA (Citosina-5-)-Metiltransferase 1 , Metilação de DNA , Decitabina , Dietilexilftalato , Psoríase , Pele , Animais , Metilação de DNA/efeitos dos fármacos , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Psoríase/imunologia , Psoríase/patologia , Decitabina/farmacologia , Decitabina/uso terapêutico , DNA (Citosina-5-)-Metiltransferase 1/antagonistas & inibidores , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Pele/patologia , Pele/efeitos dos fármacos , Pele/imunologia , Dietilexilftalato/toxicidade , Camundongos , Masculino , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Feminino

RESUMO

Dihydropyrimidines are widely recognized for their diverse biological properties and are often synthesized by the Biginelli reactions. In this backdrop, a novel series of Biginelli dihydropyrimidines were designed, synthesized, purified, and analyzed by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. Anticancer activity against MCF-7 breast cancer cells was evaluated as part of their cytotoxicity in comparison with the normal Vero cells. The cytotoxicity of dihydropyrimidines ranges from moderate to significant. Among the 38 dihydropyrimidines screened, compounds 16, 21, and 39 exhibited significant cytotoxicity. These 3 compounds were subjected to flow cytometry studies and EGFRwt Kinase inhibition assay using lapatinib as a standard. The study included evaluation for the inhibition of EGFR and HER2 expression at five different concentrations. At a concentration of 1000 nM compound 21 showed 98.51 % and 96.79 % inhibition of EGFR and HER2 expression. Moreover, compounds 16, 21 and 39 significantly inhibited EGFRwt activity with IC50 = 69.83, 37.21 and 76.79 nM, respectively. In addition, 3D-QSAR experiments were conducted to elucidate Structure activity relationships in a 3D grid space by comparing the experimental and predicted cytotoxic activities. Molecular docking studies were performed to validate the results by in silico method. All together, we developed a new series of Biginelli dihydropyrimidines as dual EGFR/HER2 inhibitors.

Assuntos

Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Simulação de Acoplamento Molecular , Inibidores de Proteínas Quinases , Pirimidinas , Receptor ErbB-2 , Humanos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-2/metabolismo , Pirimidinas/farmacologia , Pirimidinas/química , Pirimidinas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Animais , Chlorocebus aethiops , Células MCF-7 , Relação Quantitativa Estrutura-Atividade , Células Vero , Relação Estrutura-Atividade

RESUMO

Background and Objectives: Non-Hodgkin lymphoma (NHL) has the sixth-highest malignancy-related mortality in the United States (US). However, inequalities exist in access to advanced care in specific patient populations. We aim to study the racial disparities in major adverse cardiovascular and cerebrovascular events (MACCEs) in NHL patients. Materials and Methods: Using ICD-10 codes, patients with NHL were identified from the US National Inpatient Sample 2016-2019 database. Baseline characteristics, comorbidities, and MACCE outcomes were studied, and results were stratified based on the patient's race. Results: Of the 777,740 patients with a diagnosis of NHL, 74.22% (577,215) were White, 9.15% (71,180) were Black, 9.39% (73,000) were Hispanic, 3.33% (25,935) were Asian/Pacific Islander, 0.36% (2855) were Native American, and 3.54% (27,555) belonged to other races. When compared to White patients, all-cause mortality (ACM) was significantly higher in Black patients (aOR 1.27, 95% CI 1.17-1.38, p < 0.001) and in Asian/Pacific Islander patients (aOR 1.27, 95% CI 1.12-1.45, p < 0.001). Sudden cardiac death was found to have a higher aOR in all racial sub-groups as compared to White patients; however, it was statistically significant in Black patients only (aOR 1.81, 95% CI 1.52-2.16, p < 0.001). Atrial fibrillation (AF) risk was significantly lower in patients who were Black, Hispanic, and of other races compared to White patients. Acute myocardial infarction (AMI) was noted to have a statistically significantly lower aOR in Black patients (0.70, 95% CI 0.60-0.81, p < 0.001), Hispanic patients (0.69, 95% CI 0.59-0.80, p < 0.001), and patients of other races (0.57, 95% CI 0.43-0.75, p < 0.001) as compared to White patients. Conclusions: Racial disparities are found in MACCEs among NHL patients, which is likely multifactorial, highlighting the need for healthcare strategies stratified by race to mitigate the increased risk of MACCEs. Further research involving possible epigenomic influences and social determinants of health contributing to poorer outcomes in Black and Asian/Pacific Islander patients with NHL is imperative.

Assuntos

Doenças Cardiovasculares , Transtornos Cerebrovasculares , Linfoma não Hodgkin , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/etnologia , Transtornos Cerebrovasculares/mortalidade , Transtornos Cerebrovasculares/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/mortalidade , Linfoma não Hodgkin/etnologia , Grupos Raciais/estatística & dados numéricos , Estados Unidos/epidemiologia , Negro ou Afro-Americano , Brancos , Hispânico ou Latino , Nativo Asiático-Americano do Havaí e das Ilhas do Pacífico

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficiencies in communication, repetitive and stereotyped behavioral patterns, and difficulties in reciprocal social engagement. The presence of immunological dysfunction in ASD has been well established. Aflatoxin B1 (AFB1) is a prevalent mycotoxin found in food and feed, causing immune toxicity and hepatotoxicity. AFB1 is significantly elevated in several regions around the globe. Existing research indicates that prolonged exposure to AFB1 results in neurological problems. The BTBR T+ Itpr3tf/J (BTBR) mice, which were used as an autism model, exhibit the primary behavioral traits that define ASD, such as repeated, stereotyped behaviors and impaired social interactions. The main objective of this work was to assess the toxic impact of AFB1 in BTBR mice. This work aimed to examine the effects of AFB1 on the expression of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 by CD19+ B cells in the spleen of the BTBR using flow cytometry. We also verified the impact of AFB1 exposure on the mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain of BTBR mice using real-time PCR. The findings of our study showed that the mice treated with AFB1 in the BTBR group exhibited a substantial increase in the presence of CD19+Notch-1+, CD19+IL-6+, CD19+MCP-1+, CD19+iNOS+, CD19+GM-CSF+, and CD19+NF-κB p65+ compared to the mice in the BTBR group that were treated with saline. Our findings also confirmed that administering AFB1 to BTBR mice leads to elevated mRNA expression levels of Notch-1, IL-6, MCP-1, iNOS, GM-CSF, and NF-κB p65 in the brain, in comparison to BTBR mice treated with saline. The data highlight that exposure to AFB1 worsens immunological abnormalities by increasing the expression of inflammatory mediators in BTBR mice.

Assuntos

Aflatoxina B1 , Antígenos CD19 , Modelos Animais de Doenças , Animais , Camundongos , Aflatoxina B1/toxicidade , Antígenos CD19/metabolismo , Masculino , Mediadores da Inflamação/metabolismo , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/imunologia , Transtorno Autístico/metabolismo , Camundongos Transgênicos

RESUMO

This study focuses on the current applications, potential, and challenges to Artificial Intelligence (AI) integration in vascular surgery with specific emphasis on its relevance in Pakistan. Despite the benefits of AI in vascular surgery, there is a substantial gap in its adoption in Pakistan compared to global standards. In our context with limited resources and a scarcity of vascular surgeons, AI can serve as a promising solution. It can enhance healthcare accessibility, improve diagnostic accuracy, and alleviate the workload on vascular surgeons. However, hurdles including the absence of a comprehensive vascular surgery database, a shortage of AI experts, and potential algorithmic biases pose significant challenges to AI implementation. Despite these obstacles, the study underscores the imperative for continued research, collaborative efforts, and investments to unlock the full potential of AI and elevate vascular healthcare standards in Pakistan.

Assuntos

Inteligência Artificial , Procedimentos Cirúrgicos Vasculares , Paquistão , Humanos , Procedimentos Cirúrgicos Vasculares/métodos

RESUMO

Diabetes mellitus is a complex metabolic disorder resulting from the interplay of environmental, genetic, and epigenetic factors that increase the risk of cancer development. However, it is unclear whether the increased cancer risk is due to poor glycemic control or the use of some antidiabetic medications. Therefore, we investigated the genetic and epigenetic changes in somatic cells in a mouse model of diabetes and studied whether multiple exposures to the antidiabetic medication dapagliflozin influence these changes. We also elucidated the mechanism(s) of these ameliorations. The micronucleus test and modified comet assay were used to investigate bone marrow DNA damage and methylation changes. These assays revealed that dapagliflozin is non-genotoxic in the tested regimen, and oxidative DNA damage and hypermethylation were significantly higher in diabetic mice. Spectrophotometry also evaluated oxidative DNA damage and global DNA methylation, revealing similar significant alterations induced by diabetes. Conversely, the dapagliflozin-treated diabetic animals significantly reduced these changes. The expression of some genes involved in DNA repair and DNA methylation was disrupted considerably in the somatic cells of diabetic animals. In contrast, dapagliflozin treatment significantly restored these disruptions and enhanced DNA repair. The simultaneous effects of decreased oxidative DNA damage and hypermethylation levels suggest that dapagliflozin can be used as a safe antidiabetic drug to reduce DNA damage and hypermethylation in diabetes, demonstrating its usefulness in patients with diabetes to control hyperglycemia and decrease the development of its subsequent complications.

Assuntos

Compostos Benzidrílicos , Dano ao DNA , Metilação de DNA , Diabetes Mellitus Experimental , Glucosídeos , Estresse Oxidativo , Animais , Compostos Benzidrílicos/farmacologia , Glucosídeos/farmacologia , Metilação de DNA/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Masculino , Hipoglicemiantes/farmacologia , Testes para Micronúcleos , Reparo do DNA/efeitos dos fármacos , Ensaio Cometa

RESUMO

COVID-19 infections are known to cause multi-organ complications. Hematological complications like autoimmune hemolytic anemia with a positive direct antiglobulin test (DAT), are commonly encountered. However, Coombs-negative hemolytic anemia is extremely rare. We report an interesting case of an elderly female with moderate-severe acute respiratory distress syndrome in the setting of COVID-19 pneumonia-causing Coombs-negative hemolytic anemia. This patient initially presented with sudden onset abdominal pain and vomiting, found to have an incarcerated inguinal hernia with small bowel obstruction (SBO) on imaging. Additionally, labs revealed positive COVID-19 antigen test and normocytic anemia. The hospital course was complicated by worsening hemolytic anemia and thrombocytopenia requiring blood products. Extensive workup for hemolysis in this patient with no prior hematological abnormalities, was negative for DAT and other conditions associated with or causative of hemolysis. At discharge, hemolytic parameters improved and on follow-up, hemoglobin returned to baseline, and repeat hemolytic parameters were normal. This case emphasizes the importance of considering SARS-CoV-2 along with other viral infections as one of the differentials for Coombs-negative hemolytic anemia.

RESUMO

Graphene oxide (GO) has become the most attractive material for membrane technology owing to its potential application as a nanofiller in water treatment, purification, and desalination. In this study, we incorporated mica as a cross-linking reagent to increase the interlayer spacing and stability of GO sheets and fabricated a mica/GO (MGO) membrane for the first time. The MGO membrane (260 ± 10 nm) exhibits 100% rejection for biomolecules such as tannic acid (TA) and bovine serum albumin (BSA) and >99% rejection for multiple probe molecules, such as methylene blue, methyl orange, congo red, and rhodamine B. The high rejection of membranes can be attributed to the surface interaction of mica with GO nanosheets through covalent interaction, which enhances the stability and separation efficiency of the membranes for probe ions and molecules. This ultrathin MGO membrane also exhibits much better water permeability at 870 ± 5 L m-2 h-1 bar-1, which is 10-100 times greater than that reported for pure GO and GO-based composite membranes. Additionally, the membrane shows high rejection for salt ions (70%). Furthermore, the stability of the MGO membranes was evaluated under various conditions, and the membranes demonstrated remarkable stability for up to 60 days in a neutral environment.