RESUMEN
Hole-transporting materials (HTMs) are crucial for obtaining the stability and high efficiency of perovskite solar cells (PSCs). However, the current state-of-the-art n-i-p PSCs relied on the use of 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-OMeTAD) exhibit inferior intrinsic and ambient stability due to the p-dopant and hydrophilic Li-TFSI additive. In this study, a new spiro-type HTM with a critical quasi-planar core (Z-W-03) is developed to improve both the thermal and ambient stability of PSCs. The results suggest that the planar carbazole structure effectively passivates the trap states compared to the triphenylamine with a propeller-like conformation in spiro-OMeTAD. This passivation effect leads to the shallower trap states when the quasi-planar HTMs interact with the Pb-dimer. Consequently, the device using Z-W-03 achieves a higher Voc of 1.178 V compared to the spiro-OMeTAD's 1.155 V, resulting in an enhanced efficiency of 24.02%. In addition, the double-column π-π stacking of Z-W-03 results in high hole mobility (~10-4 cm2 V-1 s-1) even without p-dopant. Moreover, when the surface interface is modified, the undoped Z-W-03 device can achieve an efficiency of nearly 23%. Compared to the PSCs using spiro-OMeTAD, those with Z-W-03 exhibit enhanced stability under N2 and ambient conditions.
RESUMEN
Multiple drug resistance (MDR) has gained pronounced attention among Enterobacterales. The transfer of multiple antimicrobial resistance genes, frequently carried on conjugative incompatibility F (IncF) plasmids and facilitating interspecies resistance transmission, has been linked to Salmonella spp. and E. coli in broilers. In Egypt, the growing resistance is exacerbated by the limited clinical efficacy of many antimicrobials. In this study, IncF groups were screened and characterized in drug-resistant Salmonella spp. and E. coli isolated from broilers. The antimicrobial resistance profile, PCR-based replicon typing of bacterial isolates pre- and post-plasmid curing, and IncF replicon allele sequence typing were investigated. Five isolates of E. coli (5/31; 16.13%) and Salmonella spp. (5/36; 13.89%) were pan-susceptible to the examined antimicrobial agents, and 85.07% of tested isolates were MDR and extensively drug-resistant (XDR). Twelve MDR and XDR E. coli and Salmonella spp. isolates were examined for the existence of IncF replicons (FII, FIA, and FIB). They shared resistance to ampicillin, ampicillin/sulbactam, amoxicillin/clavulanate, doxycycline, cefotaxime, and colistin. All isolates carried from one to two IncF replicons. The FII-FIA-FIB+ and FII-FIA+FIB- were the predominant replicon patterns. FIB was the most frequently detected replicon after plasmid curing. Three XDR E. coli isolates that were resistant to 12-14 antimicrobials carried a newly FIB replicon allele with four nucleotide substitutions: C99âA, G112âT, C113âT, and G114âA. These findings suggest that broilers are a significant reservoir of IncF replicons with highly divergent IncF-FIB plasmid incompatibility groups circulating among XDR Enterobacterales. Supporting these data with additional comprehensive epidemiological studies involving replicons other than the IncF can provide insights for implementing efficient policies to prevent the spreading of new replicons to humans.
Asunto(s)
Alelos , Pollos , Farmacorresistencia Bacteriana Múltiple , Infecciones por Escherichia coli , Escherichia coli , Plásmidos , Enfermedades de las Aves de Corral , Replicón , Animales , Pollos/microbiología , Escherichia coli/genética , Escherichia coli/efectos de los fármacos , Replicón/genética , Farmacorresistencia Bacteriana Múltiple/genética , Plásmidos/genética , Enfermedades de las Aves de Corral/microbiología , Infecciones por Escherichia coli/microbiología , Infecciones por Escherichia coli/veterinaria , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Salmonella/genética , Salmonella/efectos de los fármacosRESUMEN
Objectives: To compare the outcome of botulinum toxin injection with and without glyceryl trinitrate with respect to postoperative pain and healing in the treatment of anal fissures. METHODS: The prospective, comparative study was conducted at the Department of General Surgery, Mayo Hospital, Lahore, Pakistan, from September 1, 2021, to August 31, 2022, and comprised adult chronic anal fissure patients of either gender. They were randomised using the lottery method into group A which received botulinum toxin injection, and group B which received botulinum toxin injection plus 1g of 0.2% topical glyceryl trinitrate cream. Post-operative pain was measured 24 hours after the procedure using the visual analogue scale. Healing was assessed by examining the wound for the appearance of granulation tissue 4 weeks post-procedure. Data was analysed using SPSS 26. RESULTS: Of the 88 patients, 44(50%) were in group A; 32(72.7%) males and 12(27.3%) females with mean age 33.91±14.8 years. There were 44(50%) patients in group B; 35(79.5%) males and 9(20.5%) females with mean age range 36.33±14.9 years. The mean postoperative pain at 24 hours in group A was 4.67±1.16 and it was 3.06±0.65 in group B (p=0.009). In group A, 23(69.7%) patients showed complete healing at 4 weeks compared to 30(90.9%) in group B (p=0.030). CONCLUSIONS: Botulinum toxin injection with glyceryl trinitrate could be considered as first line of treatment for chronic anal fissure in patients who refuse surgery and with previous sphincter surgery.
Asunto(s)
Toxinas Botulínicas Tipo A , Fisura Anal , Nitroglicerina , Dolor Postoperatorio , Cicatrización de Heridas , Humanos , Fisura Anal/tratamiento farmacológico , Fisura Anal/cirugía , Femenino , Masculino , Nitroglicerina/administración & dosificación , Nitroglicerina/uso terapéutico , Adulto , Dolor Postoperatorio/tratamiento farmacológico , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Persona de Mediana Edad , Enfermedad Crónica , Cicatrización de Heridas/efectos de los fármacos , Estudios Prospectivos , Adulto Joven , Vasodilatadores/administración & dosificación , Vasodilatadores/uso terapéutico , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Quimioterapia Combinada , Resultado del Tratamiento , Dimensión del DolorRESUMEN
Introduction The unique nature of a lack of good oral health, coupled with the lack of discussion and recognition surrounding the associated stigma, highlights it as a distinct issue. This stigma causes discomfort, devalues individuals, and necessitates urgent care and intervention. In Pakistan, a variety of reasons, including cultural beliefs, socioeconomic gaps, and poor access to dental care services, tend to exacerbate the stigma that is associated with dental care. This study aimed to determine the impact of stigma on oral health-seeking behaviours amongst the population of South Punjab in Pakistan. Methodology The study employed a qualitative design with a phenomenological approach, and the data collection was preceded by the administration of semi-structured interview guides and discussion guides to the patients and the consultant group, respectively. The targeted population was composed of patients who had reported stigmatization and a focus group of 10 dental consultants from various specialisations in dentistry. Data was collected until saturation from 16 patients who were recruited through the purposive convenience sampling technique. Results The study identified three themes, including perceived stigma impact on health-seeking behaviours and coping mechanisms; 10 subthemes emerged. Results showed social attitudes and unhealthy perceptions of oral conditions that lead to shame, loss of self-esteem, and lack of confidence among affected individuals. Behavioural reactions like mockery and discrimination further made it difficult for the participants who sought dental care and treatment. The study highlighted that stigma resulted in the avoidance of dental care, deterioration of oral health, and a tendency towards self-medication. People also used coping strategies such as hiding dental issues by avoiding social gatherings and seeking help from close friends to manage oral health stigma. Dental consultants had the strong opinion that care quality could be enhanced by utilising compassionate communication and patient education campaigns. Conclusions The experiences of patients and consultants related to dental stigma highlighted the complex interplay of sociocultural norms and healthcare practices. The study demonstrated that perceived stigma impacted the health-seeking behaviours of patients. Social support and education about oral health helped patients overcome this stigma. The study revealed that patients avoided dental treatments due to stigmatised behaviour from health professionals, a lack of affordability, and a feeling of shame to show and discuss the condition of their teeth, which got even worse due to self-remedy. The experiences of patients and consultants highlighted the need for increased advocacy, educational campaigns, and policies that can reduce inequalities in oral health and improve health equity. The study recommends specific intervention strategies and policy formulation to address oral health inequalities and contribute to advancing oral health equity in Pakistan.
RESUMEN
During the first several weeks following lactation, nipple pain frequently prevents mothers from continuing breastfeeding. To evaluate the efficacy of using Photobiomodulation (PBM) versus anti-inflammatory topical cream, on inflamed nipple, and the effect on milk production. This study was carried-out on 50 breastfeeding women with nipple pain and fissure. Our patients were divided into two groups ; study group (Group I): 25 patients received 12 sessions of PBM using Diode laser for a period of 4 weeks, 3 sessions per week every alternative day, and controlled group (Group II): 25 patients used Anti-inflammatory topical cream. Regarding inflammatory signs in both groups, Group I showed a significant decrease in redness compared to Group II at the 3rd and 4th week, and a significant decrease in nipple fissure and pain at the 3rd week. There was a significant increase in milk amount reflected on the infant's weight. We concluded that PBM was more effective in decreasing nipple pain, inflammation and subsequently milk production and infant weight than topical anti-inflammatory creams.
Asunto(s)
Lactancia Materna , Lactancia , Terapia por Luz de Baja Intensidad , Pezones , Humanos , Femenino , Terapia por Luz de Baja Intensidad/métodos , Pezones/efectos de la radiación , Lactancia/efectos de la radiación , Adulto , Recién Nacido , Láseres de Semiconductores/uso terapéutico , Adulto Joven , Dolor/radioterapia , Dolor/etiología , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéuticoRESUMEN
BACKGROUND: There is little international data on morbidity and mortality of surgery for perforated peptic ulcer (PPU). This study aimed to understand the global 30-day morbidity and mortality of patients undergoing surgery for PPU and to identify variables associated with these. METHOD: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022. Patients who were treated conservatively or had an underlying gastric cancer were excluded. Patients were divided into subgroups according to age (≤ 50 and > 50 years) and time from onset of symptoms to hospital presentation (≤ 24 and > 24 h). Univariate and Multivariate analyses were carried out to identify factors associated with higher 30-day morbidity and mortality. RESULTS: 1874 patients from 159 centres across 52 countries were included. 78.3% (n = 1467) of the patients were males and the median (IQR) age was 49 years (25). Thirty-day morbidity and mortality were 48.5% (n = 910) and 9.3% (n = 174) respectively. Median (IQR) hospital stay was 7 (5) days. Open surgery was performed in 80% (n = 1505) of the cohort. Age > 50 years [(OR = 1.7, 95% CI 1.4-2), (OR = 4.7, 95% CI 3.1-7.6)], female gender [(OR = 1.8, 95% CI 1.4-2.3), (OR = 1.9, 95% CI 1.3-2.9)], shock on admission [(OR = 2.1, 95% CI 1.7-2.7), (OR = 4.8, 95% CI 3.2-7.1)], and acute kidney injury [(OR = 2.5, 95% CI 1.9-3.2), (OR = 3.9), 95% CI 2.7-5.6)] were associated with both 30-day morbidity and mortality. Delayed presentation was associated with 30-day morbidity [OR = 1.3, 95% CI 1.1-1.6], but not mortality. CONCLUSIONS: This study showed that surgery for PPU was associated with high 30-day morbidity and mortality rate. Age, female gender, and signs of shock at presentation were associated with both 30-day morbidity and mortality.
Asunto(s)
Úlcera Péptica Perforada , Humanos , Úlcera Péptica Perforada/cirugía , Úlcera Péptica Perforada/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/etiología , Tiempo de Internación/estadística & datos numéricos , Salud Global , Factores de RiesgoRESUMEN
Background: Bacillus cereus (B. cereus) biofilm is grown not only on medical devices but also on different substrata and is considered a potential hazard in the food industry. Quorum sensing plays a serious role in the synthesis of biofilm with its surrounding extracellular matrix enabling irreversible connection of the bacteria. Aim: The goal of the current investigation was to ascertain the prevalence, patterns of antimicrobial resistance, and capacity for B. cereus biofilm formation in meat and meat products in Egypt. Methods: In all, 150 meat and meat product samples were used in this study. For additional bacteriological analysis, the samples were moved to the Bacteriology Laboratory. Thereafter, the antimicrobial, antiquorum sensing, and antibiofilm potential of apple cider vinegar (ACV) on B. cereus were evaluated. Results: Out of 150 samples, 34 (22.67%) tested positive for B. cereus. According to tests for antimicrobial susceptibility, every B. cereus isolates tested positive for colistin and ampicillin but negative for ciprofloxacin and imipenem. The ability to form biofilms was present in all 12 multidrug-resistant B. cereus isolates (n = 12); of these, 6 (50%), 3 (25%), and 3 (25%) isolates were weak, moderate, and strong biofilm producers, respectively. It is noteworthy that the ACV demonstrated significant inhibitory effects on B. cereus isolates, with minimum inhibitory concentrations varying between 2 and 8 µg/ml. Furthermore, after exposing biofilm-producing B. cereus isolates to the minimum biofilm inhibitory concentrations 50 of 4 µg/ml, it demonstrated good antibiofilm activity (>50% reduction of biofilm formation). Strong biofilm producers had down-regulated biofilm genes (tasA and sipW) and their regulator (plcR) compared to the control group, according to reverse transcriptase quantitative polymerase chain reaction analysis. Conclusion: Our study is the first report, that spotlights the ACV activity against B. cereus biofilm and its consequence as a strong antibacterial and antibiofilm agent in the food industry and human health risk.
Asunto(s)
Antiinfecciosos , Malus , Humanos , Animales , Bacillus cereus/genética , Ácido Acético/farmacología , Carne/microbiología , Antiinfecciosos/farmacología , BiopelículasRESUMEN
One of the most important emerging health problems is the increasing role of animals in the rapid global rise in resistance to last-resort antibiotics, such as carbapenems. However, there is limited information on the role of pet animals in harboring and spreading pandrug-resistant (PDR) carbapenemase-producing Enterobacterales (CPE), especially in Egypt. This cross-sectional study was conducted to screen for CPE in healthy and diseased pets using phenotypic and molecular methods and the NG-Test CARBA 5 immunochromatographic assay. Rectal swabs were collected from 62 dogs and 48 cats, incubated overnight in tryptic soy broth containing 10 µg of meropenem disc and subsequently cultured on MacConkey agar supplemented with meropenem (1 mg/L). Sixty-six isolates (60.6%), including 56 Klebsiella pneumoniae, seven Escherichia coli, and three K. oxytoca isolates, were confirmed to be carbapenem-resistant Enterobacterales (CRE) by the disc diffusion method, broth microdilution test, CNPt-direct, and PCR assay targeting carbapenemase genes. Forty-three (65.2%) dogs and 23 (34.8%) cats carried CPE. Of these, 35 (70.0%) were healthy (including 27 dogs and 8 cats) and 31 (52.5%) were diseased (including 16 dogs and 15 cats). bla OXA-181 was the most common gene detected (42/66, 63.6%), followed by bla IMP (40/66, 60.6%), bla OXA-48-like (29/66, 43.9%), bla KPC and bla VIM (20/66, 30.3% each), and bla NDM (17/66, 25.8%). The identified genotypes were bla KPC-2, bla IMP-1, bla VIM-1, bla NDM-1, and bla NDM-5. The CARBA 5 assay showed higher sensitivity and specificity for the detection of NDM, OXA and KPC than that for VIM and IMP genes. Antimicrobial resistance profiles of CRE isolates revealed 20 PDR, 30 extensively drug-resistant (XDR), and 16 multidrug-resistant (MDR) phenotypes. This study provides evidence of colonization with PDR CPE in dogs and cats. To manage the infection or colonization of pets in veterinary clinical settings, extended surveillance systems should be considered, and the use of critical antibiotics should be strictly controlled.
Asunto(s)
Enfermedades de los Gatos , Enfermedades de los Perros , Gatos , Perros , Animales , Estudios Transversales , Meropenem , Egipto , Pruebas de Sensibilidad Microbiana , Proteínas Bacterianas/genética , Proteínas Bacterianas/análisis , beta-Lactamasas/genética , beta-Lactamasas/análisis , Antibacterianos/farmacología , Escherichia coli/genéticaRESUMEN
Values-based medicine (VsBM) is an ethical concept, and bioethical framework has been developed to ensure that medical ethics and values are implemented, pervasive, and powerful parameters influencing decisions about health, clinical practice, teaching, medical industry, career development, malpractice, and research. Neurosurgeons tend to adopt ethics according to their own values and to what they see and learn from teachers. Neurosurgeons, in general, are aware about ethical codes and the patient's rights. However, the philosophy, concept, and principles of medical ethics are rarely included in the training programs or in training courses. The impact of implementing, observing the medical ethics and the patients' value and culture on the course, and outcome of patients' management should not underestimate. The main principles of medical ethics are autonomy, beneficence, nonmaleficence, justice, dignity, and honesty, which should be strictly observed in every step of medical practice, research, teaching, and publication. Evidence-based medicine has been popularized in the last 40-50 years in order to raise up the standard of medical practice. Medical ethics and values have been associated with the medical practice for thousands of years since patients felt a need for treatment. There is no conflict between evidence-based medicine and values-based medicine, as a medical practice should always be performed within a frame of ethics and respect for patients' values. Observing the principles of values-based medicine became very relevant as multicultural societies are dominant in some countries and hospitals in different corners of the world.
Asunto(s)
Brassicaceae , Obligaciones Morales , Humanos , Concienciación , Beneficencia , Códigos de ÉticaRESUMEN
During the COVID-19 pandemic, educational institutions confronted the possibility of complete closure and took countermeasures by adapting e-learning platforms. The present cross-sectional study quantified the impact of the pandemic on medical education using a validated and reliable tool. The tool was used to explore the perceptions of 270 healthcare students about e-learning in comparison to traditional learning systems. Inferential statistics were employed using Pearson's chi-squared test. It was found that e-learning was advantageous because of its location flexibility (46.1%) and the ease of access to study materials (46.5%). However, in-person learning was found to lead to an increase in knowledge (44.9%), clinical skills (52.7%), and social competencies (52.7%). The study concluded that while e-learning offers flexibility, traditional face-to-face teaching is deemed more effective for skill development and social interaction. Hence, e-learning should complement rather than replace traditional methods due to limitations in replicating clinical environments.
RESUMEN
BACKGROUND: The triglyceride-glucose (TyG) index was shown to be an independent predictor of coronary artery disease (CAD) progression and prognosis. However, whether the TyG index can predict the severity of CAD in nondiabetic patients with chronic coronary syndrome remains unclear. METHODS: A total of 118 individuals who underwent elective coronary angiography were classified into group A (59 with coronary lesions) and group B (59 with normal coronary arteries; as a control group) after coronary angiography and laboratory tests for fasting and the postprandial (PP) TyG index. The complexity of CAD was determined by the Synergy Between Percutaneous Coronary Intervention (SYNTAX) score (SYNTAX score >22 indicated moderate-high risk), and patients diagnosed with diabetes or prediabetes were excluded. RESULTS: The TyG index was not related to the SYNTAX score in groups A and B; however, in the CAD group with an low-density lipoprotein (LDL) concentration <70 mg/dL (group A1), a fasting TyG index ≥8.25 and a PP TyG index ≥11 could predict moderate-high SYNTAX risk score; in addition, the odds ratio (OR) was 4.3× higher and the relative risk (RR) was 1.8× greater (OR = 4.3, RR = 1.8, 95% confidence interval = 1.4-13.5, P < 0.05) for individuals with a higher fasting TyG index ≥8.25 to have a moderate-high SYNTAX risk score. Individuals with a higher PP TyG index ≥11 had OR of 2.6× higher and a RR of 1.4× greater to have moderate-high SYNTAX risk score. CONCLUSIONS: Both fasting and PP TyG levels were associated with greater coronary anatomical complexity (SYNTAX score >22) in nondiabetic chronic coronary patients with LDL <70 mg/dL. Fasting and the PP TyG indices can serve as noninvasive predictors of CAD complexity in nondiabetic patients with LDL <70 mg/dL and could change the management and therapeutic approaches.
Asunto(s)
Glucemia , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Índice de Severidad de la Enfermedad , Triglicéridos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Glucemia/análisis , Glucemia/metabolismo , Triglicéridos/sangre , Anciano , Enfermedad Crónica , Pronóstico , Valor Predictivo de las Pruebas , Biomarcadores/sangreRESUMEN
BACKGROUND: In pediatrics, shunt infection is considered the most common complication of ventriculoperitoneal (VP) shunt insertion and the main cause of shunt failure. Careful surgical technique and hygienic skin preparations are highly important for prevention of shunt infections. Our objective was to assess the significance of using preoperative chlorhexidine/alcohol as a skin antiseptic in reducing the infection rate in pediatric VP shunts surgery. METHODS: We conducted a retrospective, case control study of 80 pediatric patients with active hydrocephalus. The control group (a single step of preoperative skin antisepsis using povidone-iodine and isopropyl alcohol) comprised 40 patients who underwent a shunt surgery between January 2019 and June 2020 and the study group (two steps of preoperative skin antisepsis using 2% chlorhexidine gluconate in 70% isopropyl alcohol as a first step followed by povidone-iodine as a second step) comprised 40 patients who underwent a shunt surgery between July 2020 and January 2022. RESULTS: Shunt infection was encountered in 11 (13.7%) patients. It was significantly higher in preterm babies (p = 0.010), patients with a previous shunt revision (p < 0.001), and those with a previous shunt infection (p < 0.001). The incidence of infection was 22.5% in the control group and 5% in study group, with a statistically significant difference (p = 0.023). CONCLUSIONS: Two steps of preoperative skin antisepsis, first using chlorhexidine/alcohol and then povidone-iodine scrub solution, may significantly reduce the infection rate in pediatric VP shunt surgeries.
RESUMEN
OBJECTIVES: This study aimed to determine the normal vasculature indices of the endometrium and to correlate them with those in various physiological states. METHODS: Women undergoing ultrasound at the Feto-Maternal Center, Qatar in 2020-2021 as part of their gynecologic evaluation were enrolled into the study. They were divided into those with normal menses and no additional pathology, those following spontaneous miscarriage, postpartum and menopausal. Three-dimensional (3D) evaluation of the endometrial vasculature was done and the parameters quantified included vascularization index (VI), flow index (FI), vascularization flow index (VFI), endometrial thickness, endometrial volume and uterine volume. JASP, an open-source statistical analysis software, was used for analysis and an independent t-test to compare the vascularity indices. A multivariate regression analysis was also done to look at the factors affecting the endometrial vascular indices within the luteal phase. RESULTS: A total of 461 women were studied: 122 in the follicular phase, 199 in the luteal phase, 90 after a spontaneous miscarriage, 29 postpartum, and 16 menopausal. The vascularity indices were highest after miscarriage and lowest postnatally. There were no significant effects of age, gravida, para, or abortions on VI and VFI. However, there was a significant positive effect of age on FI (P = 0.019) There was a significant increase in endometrial volume and thickness in the luteal phase as compared to follicular phase (P < 0.01), but there was no difference in the vascularity indices. The uterine and endometrial volume in the postnatal group were nearly double that of the luteal group (P value <0.01 and 0.014, respectively). There was a significant decrease in flow index in the postnatal group compared to the luteal group (P < 0.01), suggesting low flow intensity in the postnatal group. CONCLUSIONS: Endometrial vascular indices measured using 3D Doppler can be used to determine normal vascular indices and vary with physiological states such as after miscarriages, postnatally and in the menopausal states.
Asunto(s)
Endometrio , Imagenología Tridimensional , Humanos , Femenino , Adulto , Endometrio/diagnóstico por imagen , Endometrio/irrigación sanguínea , Persona de Mediana Edad , Ultrasonografía/métodos , Menopausia , Aborto Espontáneo/diagnóstico por imagen , Embarazo , Qatar , Periodo Posparto , Adulto Joven , Menstruación/fisiologíaRESUMEN
Monoamine oxidases (MAOs) and vascular endothelial growth factor receptor-2 (VEGFR-2) are promoters of colorectal cancer (CRC) and central signaling nodes in epithelial-mesenchymal transition (EMT) induced by activating hypoxia-inducible factors (HIFs). Herein, a novel series of rationally designed triazole-tethered quinoxalines were synthesized and evaluated against HCT-116 CRC cells. The tailored scaffolds combine the pharmacophoric themes of both VEGFR-2 inhibitors and MAO inhibitors. All the synthesized derivatives were screened utilizing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay for their possible cytotoxic effects on normal human colonocytes, then evaluated for their anticancer activities against HCT-116 cells overexpressing MAOs. The hit derivatives 11 and 14 exhibited IC50 = 18.04 and 7.850 µM, respectively, against HCT-116cells within their EC100 doses on normal human colonocytes. Wound healing assay revealed their efficient CRC antimetastatic activities recording HCT-116 cell migration inhibition exceeding 75 %. In vitro enzymatic assays demonstrated that both 11 and 14 efficiently inhibited VEGFR-2 (IC50 = 88.79 and 9.910 nM), MAO-A (IC50 = 0.763 and 629.1 nM) and MAO-B (IC50 = 0.488 and 209.6 nM) with observed MAO-B over MAO-A selectivity (SI = 1.546 and 3.001), respectively. Enzyme kinetics studies were performed for both compounds to identify their mode of MAO-B inhibition. Furthermore, qRT-PCR analysis showed that the hits efficiently downregulated HIF-1α in HCT-116cells by 3.420 and 16.96 folds relative to untreated cells. Docking studies simulated their possible binding modes within the active sites of VEGFR-2 and MAO-B to highlight their essential structural determinants of activities. Finally, they recorded in silico drug-like absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles as well as ligand efficiency metrics.
Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Simulación del Acoplamiento Molecular , Estructura Molecular , Monoaminooxidasa/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Quinoxalinas/farmacología , Relación Estructura-Actividad , Triazoles/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/farmacología , Neoplasias Colorrectales/tratamiento farmacológicoRESUMEN
PURPOSE: We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. METHODS: Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). RESULTS: On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION: Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.
Asunto(s)
Acrilamidas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias del Sistema Nervioso Central , Indoles , Neoplasias Pulmonares , Pirimidinas , Humanos , Compuestos de Anilina/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Pemetrexed/uso terapéutico , Platino (Metal)/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
INTRODUCTION AND IMPORTANCE: Foot degloving injuries are serious problem and presented regularly to plastic surgery department. Proper identification of this condition followed by suitable reconstruction reduces disability and limb loss. This study highlights the effectiveness of a supramalleolar flap for covering a foot defect. CASE PRESENTATION: An 18 year- old man was involved in a road traffic accident and received trauma to his left foot which led to loss of the skin of the dorsum of his foot. He was referred to a plastic surgery unit after initial stabilization. After reassessment, he was diagnosed as a left dorsum foot degloving injury. Then he underwent multiple sessions of debridement followed by resurfacing of the foot using pedicaled lateral supramalleolar flap. The flap covers the dorsum aspect of the left foot and the post-surgery period passed uneventfully. CLINICAL DISCUSSION: The Lateral supra malleolar flap reaches distal defects, preserves a main limb neurovascular supply and is aesthetically acceptable. All these advantages, besides ease of harvest, make it more useful for cover of foot defects. Although it is not an ideal reconstructive method, when microvascular surgery is not applicable, this technique will cover foot defects. CONCLUSION: We present this case because foot degloving injury is common but there is limited options for covering, although free flap is gold standard reconstructive tool but pedicaled supramalleolar flap can reach final result similar to complex surgeries. Although complications exist in literature, benefits promote using this method.
RESUMEN
Pseudomonas aeruginosa is notorious for its ability to develop a high level of resistance to antimicrobial agents. Resistance-nodulation-division (RND) efflux pumps could mediate drug resistance in P. aeruginosa. The present study aimed to evaluate the antibacterial and anti-efflux activities of cinnamon essential oil either alone or combined with ciprofloxacin against drug resistant P. aeruginosa originated from human and animal sources. The results revealed that 73.91% of the examined samples were positive for P. aeruginosa; among them, 77.78% were of human source and 72.73% were recovered from animal samples. According to the antimicrobial resistance profile, 48.73% of the isolates were multidrug-resistant (MDR), 9.2% were extensive drug-resistant (XDR), and 0.84% were pan drug-resistant (PDR). The antimicrobial potential of cinnamon oil against eleven XDR and one PDR P. aeruginosa isolates was assessed by the agar well diffusion assay and broth microdilution technique. The results showed strong antibacterial activity of cinnamon oil against all tested P. aeruginosa isolates with inhibition zones' diameters ranging from 34 to 50 mm. Moreover, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of cinnamon oil against P. aeruginosa isolates ranged from 0.0562-0.225 µg/mL and 0.1125-0.225 µg/mL, respectively. The cinnamon oil was further used to evaluate its anti-efflux activity against drug-resistant P. aeruginosa by phenotypic and genotypic assays. The cartwheel test revealed diminished efflux pump activity post cinnamon oil exposure by two-fold indicating its reasonable impact. Moreover, the real-time quantitative polymerase chain reaction (RT-qPCR) results demonstrated a significant (p < 0.05) decrease in the expression levels of MexA and MexB genes of P. aeruginosa isolates treated with cinnamon oil when compared to the non-treated ones (fold changes values ranged from 0.4204-0.7474 for MexA and 0.2793-0.4118 for MexB). In conclusion, we suggested the therapeutic use of cinnamon oil as a promising antibacterial and anti-efflux agent against drug-resistant P. aeruginosa.
RESUMEN
Aim: International guidelines on the use of anti-thrombotic therapies in left-sided ablations other than atrial fibrillation (AF) are lacking. The data regarding antiplatelet or anticoagulation strategies after catheter ablation (CA) procedures mainly derive from AF, whereas for the other arrhythmic substrates, the anti-thrombotic approach remains unclear. This survey aims to explore the current practices regarding antithrombotic management before, during, and after left-sided endocardial ablation, not including atrial fibrillation (AF), in patients without other indications for anti-thrombotic therapy. Material and Methods: Electrophysiologists were asked to answer a questionnaire containing questions on antiplatelet (APT) and anticoagulation therapy for the following left-sided procedures: accessory pathway (AP), atrial (AT), and ventricular tachycardia (VT) with and without structural heart disease (SHD). Results: We obtained 41 answers from 41 centers in 15 countries. For AP, before ablation, only four respondents (9.7%) used antiplatelets and two (4.9%) used anticoagulants. At discharge, APT therapy was prescribed by 22 respondents (53.7%), and oral anticoagulant therapy (OAC) only by one (2.4%). In patients with atrial tachycardia (AT), before ablation, APT prophylaxis was prescribed by only four respondents (9.7%) and OAC by eleven (26.8%). At discharge, APT was recommended by 12 respondents (29.3%) and OAC by 24 (58.5%). For VT without SHD, before CA, only six respondents (14.6%) suggested APT and three (7.3%) suggested OAC prophylaxis. At discharge, APT was recommended by fifteen respondents (36.6%) and OAC by five (12.2%). Regarding VT in SHD, before the procedure, eight respondents (19.5%) prescribed APT and five (12.2%) prescribed OAC prophylaxis. At discharge, the administration of anti-thrombotic therapy depended on the LV ejection fraction for eleven respondents (26.8%), on the procedure time for ten (24.4%), and on the radiofrequency time for four (9.8%), with a cut-off value from 1 to 30 min. Conclusions: Our survey indicates that the management of anti-thrombotic therapy surrounding left-sided endocardial ablation of patients without other indications for anti-thrombotic therapy is highly variable. Further studies are necessary to evaluate the safest approach to these procedures.