RESUMEN
BACKGROUND: The magnitude of MDR-TB cases was noticeable in Egypt. However, the last national survey was 11-years ago. The current survey was conducted to determine the prevalence of rifampicin resistance among sputum smear-positive pulmonary tuberculosis patients in Egypt. METHODS: A national health facility-based cross-sectional study was conducted in 14 randomly selected governorates in Egypt between August 2020 and September 2021. All presumptive TB cases, either new or previously treated according to WHO definitions, with no gender, age, or nationality limitations, and provided informed consent were included in the study. Each patient completed a case report form (CRF). The CRF included socio-demographic and clinical data. Sputum samples were collected according to standard techniques and cultured on Lowenstein-Jensen (L-J) medium. Gene X-pert test was carried out first on the samples for simultaneous identification of MTB and rifampicin resistance. The prevalence of RR was calculated using crude, cluster, and weighted methods. Factors associated with RR were analyzed by bivariate and multivariate techniques. RESULTS: Among the total 849 presumptive TB patients enrolled in the study, 710 (83.6%) patients were subjected to Gene X-pert testing (MTB/RIF). The crude prevalence of RR was 3.32% (95% CI: 1.89-4.76%) among the new cases and 9.46% (95% CI: 2.63-16.29%) among the retreated cases with an overall estimate of 3.99%; (95% CI: 2.51-5.47%). By cluster analysis the overall prevalence of RR was 5.01% (95% CI: 2.90-7.13). Factors associated with the prevalence of RR were co-morbidity with bronchial asthma, drug abuse and history of contact with a family member with TB. CONCLUSION: The prevalence of RR among either new or retreated cases TB patients was lower than the previous Egyptian rates in 2010-2012. The strongest predictor associated with RR was comorbidity with bronchial asthma.
Asunto(s)
Asma , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Rifampin/farmacología , Rifampin/uso terapéutico , Egipto/epidemiología , Mycobacterium tuberculosis/genética , Prevalencia , Estudios Transversales , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Instituciones de Salud , EsputoRESUMEN
BACKGROUND: Hypertensive patients are more susceptible to develop hypotension after the induction of general anesthesia (GA), most likely due to hypovolemia. An inferior vena cava collapsibility index (IVCCI) > 40-50% can predict hypotension after the induction of GA in the general population by variable accuracies. The current study aimed to investigate IVCCI% as a predictor of postinduction hypotension in hypertensive patients undergoing noncardiac surgery. METHODS: Ultrasound IVCCI % was assessed for all controlled hypertensive patients immediately before induction of GA. After induction of GA, patients were diagnosed with postinduction hypotension if their systolic arterial pressure (SAP) dropped by ≥ 30% of the baseline value and/or mean arterial pressure (MAP) dropped to < 65 mmHg up to 15 min after intubation. The receiver operating characteristic (ROC) curve of IVCCI% was compared to patients' classification either developing hypotension after induction of GA or not as a gold standard. RESULTS: Of the 153 patients who completed the study, 62 (40.5%) developed hypotension after the induction of GA, and 91 (59.5%) did not. An IVCCI > 39% predicted the occurrence of postinduction hypotension with high accuracy (84%) (AUC 0.908, P < 0.001). The area of uncertainty (by gray zone analysis) of IVCCI lies at values from 39 to 45%. This gray zone included 21 patients (13.7% of all patients). CONCLUSION: An inferior vena cava collapsibility index > 39% before anesthetic induction can be a simple noninvasive reliable predictor of hypotension after the induction of GA for hypertensive patients not treated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and undergoing noncardiac surgery. TRIAL REGISTRATION: This clinical trial was approved by the Institutional Review Board (IRB) at Zagazig University (ZUIRB #9424 dated 03/04/2022), and patients' informed consent for participation in the study was obtained during the period from May 2022 to May 2023. All study procedures were carried out in accordance with the ethical standards of the Helsinki Declaration of 2013.
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Hipotensión , Vena Cava Inferior , Humanos , Anestesia General/efectos adversos , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Hipotensión/inducido químicamente , Hipotensión/diagnóstico , Vena Cava Inferior/diagnóstico por imagenRESUMEN
The widespread use of pesticides is beneficial for food production; however, there are numerous adverse consequences reported in the ecosystem and humans associated with exposure to these contaminants. The pyrethriod bifenthrin (BIF) is utilized for (1) maintenance, growth, and storage of agricultural products; (2) control of internal and external parasites of farm animals; and (3) eradication of insects threatening public health. Numerous data are available regarding environmental and ecological impact of pyrethriods on the central and peripheral nervous systems; however few studies focused on non-target tissues especially in humans. Therefore, the aim of this investigation was to determine the potential cytotoxic effects of BIF on a non-target tissue using human colorectal HCT-116 cells as a model. Data demonstrated that BIF reduced cell viability and disrupted mitochondrial functions which were accompanied by increased reactive oxygen species (ROS) levels indicating the presence of oxidative stress. BIF produced a significant elevation in levels of malondialdehyde (MDA) supporting the role of oxidative stress in pesticide-mediated toxicity. Concomitantly, a fall of mitochondrial transmembrane potential (Δψ), consequently producing perturbation of fluidity as well as excitability of cellular membranes was noted. Our results also indicated that BIF induced a rise in DNA damage as evidenced by the comet assay. An increase in mitogen-activated protein kinases (MAPKs), JNK (N-terminal Kinase), p38, and ERK (extracellular-signal-regulated kinase) suggested an apoptotic effect. Data thus indicated that BIF-induced cytotoxicity in human colorectal HCT-116 cells was associated with oxidative stress, mitochondrial dysfunction, and apoptosis.
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Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/inducido químicamente , Daño del ADN/efectos de los fármacos , Células HCT116/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Plaguicidas/toxicidad , Piretrinas/toxicidad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The mycotoxin citrinin (CTN) is a natural contaminant of various human foods that may produce serious adverse health problems. Several studies demonstrated that citrinin exerts cytotoxic and genotoxic effects in both in vivo and in vitro systems. However, the precise mechanisms of action (MOA), particularly in intestinal cells remain unclear. The aim of the present study was to examine the precise MOA of citrinin in vitro. Data demonstrated that CTN significantly decreased the number of viable human intestinal HCT116 cells and induced apoptotic events including (1) decrease in ΔÑ°m indicative of mitochondrial membrane permeabilization, (2) activation of caspase 3, (3) elevated production of reactive oxygen species (ROS) and (4) relative persistence of plasma membrane integrity. Further, the genetic deficiency of the pro-apoptotic protein Bax protected cells against CTN-induced apoptosis, indicating that Bax is required for CTN-mediated toxicity. It was also found that CTN triggered endoplasmic reticulum (ER) stress and activated different arms of the unfolded protein response (UPR) as demonstrated by increase in expression of GRP78 (glucose-regulated protein-78), GRP94 (glucose-regulated protein-94), GADD34 (growth arrest and DNA damage-inducible protein-34), the protein disulfide isomerase associated 6 (PDIA6), CHOP (C/EBP-homologous protein) and the splicing of XBP1 (X-Box Binding Protein 1). Pretreatment of cells with the chemical chaperone 4-phenylbutyrate (PBA), known to alleviate ER stress, prevented significantly the apoptotic process triggered by CTN. Taken together, these results suggest that CTN exerts its cytotoxic effects in HCT116 cells by inducing apoptosis, at least in part, through induction of ER stress.
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Apoptosis/efectos de los fármacos , Citrinina/farmacología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Células HCT116 , HumanosRESUMEN
PURPOSE: Gadolinium-based contrast agents (GBCAs) may add value to magnetic resonance (MR)-only radiotherapy (RT) workflows including on hybrid machines such as the MR Linac. The impact of GBCAs on RT dose distributions however have not been well studied. This work used retrospective GBCA-enhanced datasets to assess the dosimetric effect of GBCAs on head and neck plans. METHODS: Ten patients with oropharyngeal squamous cell carcinoma receiving RT from November 2018 to April 2020 were included in this study. RT planning included contrast-enhanced computed tomography (CT) and MR scans. A contrast agent "contour" was defined by delineating GBCA-enhanced regions using an agreed window/level threshold, transferred to the planning CT and given a standardized electron density (ED) of 1.149 in the Monaco treatment planning system (Elekta AB). Four plans were per patient calculated and compared using two methods: (1) optimized without contrast (Plan A) then recalculated with ED (Plan B), and (2) optimized with contrast ED (Plan C) then without (Plan D). For target parameters minimum and maximum doses to 1cc of PTVs, D95 values, and percent dose differences were calculated. Dose differences for organs-at-risk (OARs) were calculated as a percentage of the clinical tolerance value. For the purposes of this study, ±2% over the whole treatment course was considered to be a clinically acceptable dose deviation. Wilcoxon-signed rank tests were used to determine any dose differences within and between the two methods of optimization and recalculation (p < 0.05). Pearson's correlations were used to establish the relationship between gadolinium uptake volume in a structure (i.e., proportion of structure covered by a density override) and the resulting dose difference. RESULTS: The median percent dose differences for key reportable dosimetric parameters between non-contrast and simulated contrast plans were <1.2% over all fractions over all patients for reportable target parameters (mean 0.34%, range 0.22%-1.02%). The percent dose differences for maximum dose to 1cc of both PTV1 and PTV2 were significantly different after application of density override (p < 0.05) but only in method 2 (Plan C vs. Plan D). For D95 PTV1, there was a statistically significant effect of density override (p < 0.01), however only in method 1 (Plan A vs. Plan B). There were no significant differences between calculation methods of the impact of contrast in most target parameters with the exception of D95 PTV1 (p < 0.01) and for D95 PTV2 (p < 0.05). The median percent dose differences for reportable OAR parameters as a percentage of clinical planning tolerances were <2.0% over a full treatment course (mean 0.65%, range 0.27%-1.62%). There were no significant differences in dose to OARs within or between methods for contrast impact assessment. CONCLUSIONS: Dose differences to targets and OARs in oropharyngeal cancer treatment due to the presence of GBCA were minimal, and this work suggests that prospective in vivo evaluations of impact may not be necessary in this clinical site. Accounting for GBCAs may not be needed in daily adaptive workflows on the MR Linac.
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Gadolinio , Radioterapia de Intensidad Modulada , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Órganos en Riesgo , Estudios Prospectivos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Estudios RetrospectivosRESUMEN
Environmental toxicants such as phthalate have been involved in multiple health disorders including renal diseases. Oxidative damage is implicated in many alterations caused by phthalate especially the di(2-ethylhexyl) phthalate (DEHP), which is the most useful phthalate. However, information regarding its mechanism of renal damage is lacking. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates gene expression implicated in free radical scavenging and cytoprotection including the antioxidant glutathione (GSH) pathway. The aim of this study was to assess whether DEHP affects the Nrf2 pathway and the GSH concentration. Mice were divided into four groups: a control group and three groups treated with DEHP at different concentrations (5, 50, and 200 mg/kg body weight) for 30 days. Our results showed that DEHP altered the normal levels of serum biochemical parameters creatinine (CREA), urea, and lactate dehydrogenase (LDH). This phthalate caused oxidative damage through the induction of lipid peroxidation and protein oxidation as marked by increase of protein carbonyl (PC) and loss of protein-bound sulfhydryls (PSH). Simultaneously, DEHP treatment decreased the protein level of Nrf-2, HO-1, and GCLC (responsible of GSH synthesis) and decreased the GSH level. Inhibition of the Nrf2 pathway is related to the activation of the mitochondrial pathway of apoptosis. This apoptotic process is evidenced by an upregulation of p53 and Bax protein levels in addition to a downregulation of Bcl-2. Collectively, our data demonstrated that depletion of Nrf2 and GSH was associated with the elevation of oxidative stress and the activation of intrinsic apoptosis in mouse kidney treated with DEHP.
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Dietilhexil Ftalato/toxicidad , Glutatión/metabolismo , Homeostasis , Riñón/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Biomarcadores/sangre , Glutamato-Cisteína Ligasa/metabolismo , Hemo-Oxigenasa 1/metabolismo , Homeostasis/efectos de los fármacos , Riñón/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Ratones Endogámicos BALB C , Oxidación-Reducción , Carbonilación Proteica/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Compuestos de Sulfhidrilo/metabolismoRESUMEN
This study aimed to investigate the protective effects of Eugenol (EUG), an effective antioxidant phenolic compound with a radical scavenging activity against citrinin (CTN)-induced toxicity in vitro using HCT116 cells. CTN is a well-known mycotoxin found in different constituents of the food chain. This environmental contaminant produces free radicals which interacts with cellular macromolecules and produces oxidation of protein, lipid, and DNA. The cytotoxic effects were monitored by measuring cell viability, reactive oxygen species (ROS) generation, antioxidant enzyme activities, malondialdehyde (MDA) production, protein oxidation, and DNA fragmentation. Our results have shown that the pretreatment of HCT116 cells with EUG, 2 h prior to citrinin (CTN) exposure, significantly decreased CTN-induced cell death, inhibited ROS generation, modulated activities of both catalase (CAT) and superoxide dismutase (SOD), and reduced MDA production. Level of protein-bound sulfhydryls and DNA fragmentation were also declined as compared with CTN-treated cells. These findings suggest that EUG would be an effective protective agent against CTN-induced oxidative stress, and thereby, it may complement and add to the functions of antioxidant vitamins and enzymes as a protection against the cytotoxicity of this mycotoxin.