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Cerebral ischemic stroke and glioma are the two leading causes of patient mortality globally. Despite physiological variations, 1 in 10 people who have an ischemic stroke go on to develop brain cancer, most notably gliomas. In addition, glioma treatments have also been shown to increase the risk of ischemic strokes. Stroke occurs more frequently in cancer patients than in the general population, according to traditional literature. Unbelievably, these events share multiple pathways, but the precise mechanism underlying their co-occurrence remains unknown. Transcription factors (TFs), the main components of gene expression programmes, finally determine the fate of cells and homeostasis. Both ischemic stroke and glioma exhibit aberrant expression of a large number of TFs, which are strongly linked to the pathophysiology and progression of both diseases. The precise genomic binding locations of TFs and how TF binding ultimately relates to transcriptional regulation remain elusive despite a strong interest in understanding how TFs regulate gene expression in both stroke and glioma. As a result, the importance of continuing efforts to understand TF-mediated gene regulation is highlighted in this review, along with some of the primary shared events in stroke and glioma.
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Neoplasias Encefálicas , Glioma , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Glioma/complicações , Glioma/genética , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/genética , Acidente Vascular Cerebral/genéticaRESUMO
Cancer as a disease possess quite complicated pathophysiological implications and is among the prominent causes of morbidity and mortality on global scales. Anti-cancer chemotherapy, surgery, and radiation therapy are some of the present-day conventional treatment options. However, these therapeutic paradigms own several retreats, including lack of specificity, non-targeted toxicological implications, inefficient drug delivery to targeted cells, and emergence of cancer resistance, ultimately causing ineffective cancer management. Owing to the advanced and better biophysical characteristic features and potentiality for the tailoring and customizations and in several fashions, nanotechnology can entirely transubstantiate the cancer identification and its managements. Additionally, nanotechnology also renders several answers to present-day mainstream limitations springing-up in anti-cancer therapeutics. Nanocarriers, owing to their outstanding physicochemical features including but not limited to their particle size, surface morphological features viz. shape etc., have been employed in nanomedicinal platforms for targeting various transcription factors leading to worthy pharmacological outcomes. This transcription targeting activates the wide array of cellular and molecular events like antioxidant enzyme-induction, apoptotic cell death, cell-cycle arrest etc. These outcomes are obtained after the activation or inactivation of several transcription factors and cellular pathways. Further, nanoformulations have been precisely calibrated and functionalized with peculiar targeting groups for improving their efficiency to deliver the drug-payload to specified and targeted cancerous cells and tissues. This review undertakes an extensive, across-the-board and all-inclusive approach consisting of various studies encompassing different types of tailored and customized nanoformulations and nanomaterials designed for targeting the transcription factors implicated in the process of carcinogenesis, tumor-maturation, growth and metastasis. Various transcription factors viz. nuclear factor kappa (NF-κB), signal transducer and activators of transcription (STAT), Cmyc and Twist-related protein 1 (TWIST1) along with several types of nanoparticles targeting these transcription factors have been summarized here. A section has also been dedicated to the different types of nanoparticles targeting the hypoxia inducing factors. Efforts have been made to summarize several other transcription factors implicated in various stages of cancer development, growth, progression and invasion, and their targeting with different kinds of nanomedicinal agents.
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Antineoplásicos , Neoplasias , Humanos , Nanomedicina , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antineoplásicos/química , Fatores de Transcrição , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
BACKGROUND: Evidence suggests common pathways between pregnancy losses and subsequent long-term maternal morbidity, rendering pregnancy complications an early chronic disease marker. There is a plethora of studies exploring associations between miscarriage and stillbirth with long-term adverse maternal health; however, these data are inconclusive. METHODS AND FINDINGS: We systematically searched MEDLINE, EMBASE, AMED, BNI, CINAHL, and the Cochrane Library with relevant keywords and MeSH terms from inception to June 2023 (no language restrictions). We included studies exploring associations between stillbirth or miscarriage and incidence of cardiovascular, malignancy, mental health, other morbidities, and all-cause mortality in women without previous pregnancy loss. Studies reporting short-term morbidity (within a year of loss), case reports, letters, and animal studies were excluded. Study selection and data extraction were performed by 2 independent reviewers. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS) and publication bias with funnel plots. Subgroup analysis explored the effect of recurrent losses on adverse outcomes. Statistical analysis was performed using an inverse variance random effects model and results are reported as risk ratios (RRs) with 95% confidence intervals (CIs) and prediction intervals (PIs) by combining the most adjusted RR, odds ratios (ORs) and hazard ratios (HRs) under the rare outcome assumption. We included 56 observational studies, including 45 in meta-analysis. There were 1,119,815 women who experienced pregnancy loss of whom 951,258 had a miscarriage and 168,557 stillbirth, compared with 11,965,574 women without previous loss. Women with a history of stillbirth had a greater risk of ischaemic heart disease (IHD) RR 1.56, 95% CI [1.30, 1.88]; p < 0.001, 95% PI [0.49 to 5.15]), cerebrovascular (RR 1.71, 95% CI [1.44, 2.03], p < 0.001, 95% PI [1.92, 2.42]), and any circulatory/cardiovascular disease (RR 1.86, 95% CI [1.01, 3.45], p = 0.05, 95% PI [0.74, 4.10]) compared with women without pregnancy loss. There was no evidence of increased risk of cardiovascular disease (IHD: RR 1.11, 95% CI [0.98, 1.27], 95% PI [0.46, 2.76] or cerebrovascular: RR 1.01, 95% CI [0.85, 1.21]) in women experiencing a miscarriage. Only women with a previous stillbirth were more likely to develop type 2 diabetes mellitus (T2DM) (RR: 1.16, 95% CI [1.07 to 2.26]; p < 0.001, 95% PI [1.05, 1.35]). Women with a stillbirth history had an increased risk of developing renal morbidities (RR 1.97, 95% CI [1.51, 2.57], p < 0.001, 95% [1.06, 4.72]) compared with controls. Women with a history of stillbirth had lower risk of breast cancer (RR: 0.80, 95% CI [0.67, 0.96], p-0.02, 95% PI [0.72, 0.93]). There was no evidence of altered risk of other malignancies in women experiencing pregnancy loss compared to controls. There was no evidence of long-term mental illness risk in women with previous pregnancy losses (stillbirth: RR 1.90, 95% CI [0.93, 3.88], 95% PI [0.34, 9.51], miscarriage: RR 1.78, 95% CI [0.88, 3.63], 95% PI [1.13, 4.16]). The main limitations include the potential for confounding due to use of aggregated data with variable degrees of adjustment. CONCLUSIONS: Our results suggest that women with a history of stillbirth have a greater risk of future cardiovascular disease, T2DM, and renal morbidities. Women experiencing miscarriages, single or multiple, do not seem to have an altered risk.
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Aborto Espontâneo , Mortalidade Materna , Natimorto , Humanos , Feminino , Gravidez , Aborto Espontâneo/epidemiologia , Natimorto/epidemiologia , Fatores de RiscoRESUMO
Stroke is a major contributor to mortality and impairment on a global scale, with few effective treatments available. Aberrant expression of various non-coding RNAs (ncRNAs) has been identified after stroke onset, impacting neurogenesis, angiogenesis, apoptosis, and autophagy. The roles and mechanisms of ncRNAs hold great promise for future ischemic stroke treatments, as they could modify stroke impact and course on a well-controllable molecular level. Exploring the functions and underlying mechanisms of ncRNAs after stroke has the potential to unveil novel therapeutic targets for the treatment of stroke and may also pave the way toward novel and more precise diagnostic options for stroke and stroke outcomes. This review emphasizes the importance of ncRNAs in the treatment of stroke and their potential as therapeutic targets.
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AVC Isquêmico , RNA Longo não Codificante , Acidente Vascular Cerebral , Humanos , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/terapia , Neurogênese/genéticaRESUMO
Due to the its high abundance, iron ion contamination and toxicity is one of the most challenging issue for living beings. Although, iron is extremenly important for several body functions, excess amount of iron in the body can also be fatal. In last century, rapid industrialization, iron extraction and mismanagement of industrial waste disposal leads to iron contamination in water bodies. Therefore, versatile iron sensors needs to be develop which can be employed for detection in biological as well as real water samples. 8-hydroxyquinoline is well-known for its strong affinity towards transition metals including Fe3+. In this regard, we have synthesised benzothiazole-quinoline derived 1,2,3- triazole (4HBTHQTz), in which 4-(benzo[d]thiazol-2-yl)phenolic (4-HBT) group acts as a fluorophore. 4HBTHQTz showed high fluorescence and induced a selective decrease in fluorescence with Fe3+ at 380 nm (λex. = 320 nm). The detection limit of 4HBTHQTz with Fe3+ is calculated as 0.64 µM, which is lower than the WHO recommended limit in drinking water. 4HBTHQTz works over the 5-8 pH range and has shown promising results for quantitative detection of Fe3+ in water samples collected from tap, river and seawater. 4HBTHQTz can also detect the Fe3+ in biological samples which is confirmed by fluorescence cell imaging using L929 mouse fibroblast cells. Overall, 4HBTHQTz showed advantages such as high selectivity, quick detection, and good limit of detection (LOD) for Fe3+.
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The therapeutic action of carbon monoxide (CO) is very well known and has been studied on various types of tissues and animals. However, real-time spatial and temporal tracking and release of CO is still a challenging task. This paper reported an amphiphilic CO sensing probe NP and phospholipid 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) based nanoscale vesicular sensing system Ves-NP consisting of NP. The liposomal sensing system (Ves-NP) showed good selectivity and sensitivity for CO without any interference from other relevant biological analytes. Detection of CO is monitored by fluorescence OFF-ON signal. Ves-NP displayed LOD of 5.94 µM for CO detection with a response time of 5 min. Further, in a novel attempt, Ves-NP is co-embedded with the amphiphilic CO-releasing molecule 1-Mn(CO)3 to make an analyte replacement probe Ves-NP-CO. Having a both CO releasing and sensing moiety at the surface of the same liposomal system Ves-NP-CO play a dual role. Ves-NP-CO is used for the simultaneous release and recognition of CO that can be controlled by light. Thus, in this novel approach, for the first time we have attached both the release and recognition units of CO in the vesicular surface, both release and recognition simultaneously monitored by the change in fluorescent OFF-ON signal.
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Monóxido de Carbono , Lipossomos , Animais , Fosfolipídeos , FluorescênciaRESUMO
BACKGROUND: This study delves into the complex interplay among prostate-specific antigen, alkaline phosphatase, and the temporal dynamics of tumor shrinkage in prostate cancer. By investigating the longitudinal trajectories and time-to-prostate cancer tumor shrinkage, we aim to untangle the intricate patterns of these biomarkers. This understanding is pivotal for gaining profound insights into the multifaceted aspects of prostate cancer progression. The joint model approach serves as a comprehensive framework, facilitating the elucidation of intricate interactions among these pivotal elements within the context of prostate cancer . METHODS: A new joint model under a shared parameters strategy is proposed for mixed bivariate longitudinal biomarkers and event time data, for obtaining accurate estimates in the presence of missing covariate data. The primary innovation of our model resides in its effective management of covariates with missing observations. Built upon established frameworks, our joint model extends its capabilities by integrating mixed longitudinal responses and accounting for missingness in covariates, thus confronting this particular challenge. We posit that these enhancements bolster the model's utility and dependability in real-world contexts characterized by prevalent missing data. The main objective of this research is to provide a model-based approach to get full information from prostate cancer data collected with patients' baseline characteristics ( Age , body mass index ( BMI ), GleasonScore , Grade , and Drug ) and two longitudinal endogenous covariates ( Platelets and Bilirubin ). RESULTS: The results reveal a clear association between prostate-specific antigen and alkaline phosphatase biomarkers in the context of time-to-prostate cancer tumor shrinkage. This underscores the interconnected dynamics of these key indicators in gauging disease progression. CONCLUSIONS: The analysis of the prostate cancer dataset, incorporating a joint evaluation of mixed longitudinal prostate-specific antigen and alkaline phosphatase biomarkers alongside tumor status, has provided valuable insights into disease progression. The results demonstrate the effectiveness of the proposed joint model, as evidenced by accurate estimates. The shared variables associated with both longitudinal biomarkers and event times consistently deviate from zero, highlighting the robustness and reliability of the model in capturing the complex dynamics of prostate cancer progression. This approach holds promise for enhancing our understanding and predictive capabilities in the clinical assessment of prostate cancer.
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Fosfatase Alcalina , Progressão da Doença , Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Fosfatase Alcalina/sangue , Humanos , Estudos Longitudinais , Neoplasias da Próstata/patologia , Neoplasias da Próstata/sangue , Antígeno Prostático Específico/sangue , Idoso , Fatores de Tempo , Pessoa de Meia-Idade , Carga TumoralRESUMO
AIM: To explore the core competencies needed on part of the medical and dental teachers to carry out effective digital teaching for their students. METHODS: It was a qualitative study which employed phenomenological approach. The data were collected from 12 teachers who were purposively selected for semi-structured interviews. They were all expert digital teachers. The data were transcribed verbatim, coded and analyzed thematically. Textural and structural description of the themes helped to develop a new competency framework. RESULTS: The data yielded 47 selective codes with 15 sub-themes and five themes. The emergent themes included general digital competencies, specific digital teaching competencies, mastery of the subject matter, mastery of pedagogical strategies and proficiency in using innovative digital technologies for teaching. The themes 1, 2 and 5 relate to digital competencies only whereas the themes 3 and 4 are generic competencies which apply to both digital and non-digital teaching. These generic competencies form the basis of all kinds of teaching, hence equally important for digital teaching. CONCLUSION: Medical teachers should possess diverse digital competencies. The competency framework that emerged in the current research encompasses the essential attributes that should be included in any future training program aiming at the digital capacity building of the teachers. This will keep them primed for effective digital teaching. Given its crucial importance, the digital teaching competency should be considered as a cross-cutting competency that applies to almost all of the famous eight roles of medical teacher.
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BACKGROUND: The ever-evolving healthcare system of today demands physicians who steer their roles as treatment providers, managers and collaborators. Professionals are highly interdependent due to increased complexity of health problems and risk of errors increases with transitions in care. In hospitals, the main workforce is postgraduate residents; therefore, intraprofessional collaboration amongst residents is essential. Several instruments are available to evaluate interprofessional collaboration amongst physicians, nurses and hospital teams but none specifically assessed intra-professional collaborative practices amongst residents working in tertiary care hospitals in multi-disciplinary teams. This study intends to develop and validate an instrument to self-assess intraprofessional collaborative practices in postgraduate residents undergoing residency in multiple specialties at tertiary care hospitals. APPROACH: This study on Instrument Development employed mixed method study design executed in two phases. In phase 1, six domains of intraprofessional collaborative practices were identified from literature and 35 items were developed. Fifteen experts participated in qualitative content validation and provided comments. To establish content validity in phase 2, content validity index (CVI) and content clarity average (CCA) were assessed by seventeen experts. Response process validity was established by cognitive interviewing of 5 postgraduate residents. Pilot testing was done on a sample of 407 residents. Cronbach's alpha was determined, and confirmatory factor analysis established construct validity. RESULTS: During phase 1, items were modified based on qualitative feedback from 15 experts. In round 2, CVI and CCA were determined based on responses of 17 experts. The items having an I-CVI greater than 0.90 were accepted and six items underwent modifications as their I-CVI fell between 0.78 and 0.90. Similarly, four items with a CCA of less than 2.4 were modified to increase clarity. Cognitive interviews of participants on 30 items resulted in the deletion of 1 item and changes in 5 items. The final instrument had 29 items categorized under six constructs. All items had good factor loadings during CFA, so none was deleted. Cronbach's Alpha α was 0.937. CONCLUSION: Intraprofessional collaborative practices in residents is a valid and reliable self-assessment tool comprising 29 items measuring six constructs. It may be used by residents to assess their collaborative practices and incorporated in curricula to help develop collaborative practices and their assessment during training of postgraduate residents.
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Comportamento Cooperativo , Internato e Residência , Autoavaliação (Psicologia) , Centros de Atenção Terciária , Humanos , Relações Interprofissionais , Reprodutibilidade dos Testes , Educação de Pós-Graduação em Medicina , Feminino , Masculino , Inquéritos e Questionários , Equipe de Assistência ao PacienteRESUMO
BACKGROUND: History taking and clinical reasoning are important skills that require knowledge, cognition and meta-cognition. It is important that a trainee must experience multiple encounters with different patients to practice these skills. However, patient safety is also important, and trainees are not allowed to handle critically ill patients. To address this issue, a randomized controlled trial was conducted to determine the effectiveness of using Virtual Patients (VP) versus Standardized Patients (SP) in acquiring clinical reasoning skills in ophthalmology postgraduate residents. METHODS: Postgraduate residents from two hospitals in Lahore, Pakistan, were randomized to either the VP group or the SP group and were exposed to clinical reasoning exercise via the VP or SP for 30 min after the pretest. This was followed by a posttest. One month after this activity, a follow-up posttest was conducted. The data were collected and analysed using IBM-SPSS version 25. Repeated measures ANOVA was used to track the effect of learning skills over time. RESULTS: The mean age of the residents was 28.5 ± 3 years. The male to female ratio was 1:1.1. For the SP group, the mean scores were 12.6 ± 3.08, 16.39 ± 3.01 and 15.39 ± 2.95, and for the VP group, the mean scores were 12.7 ± 3.84, 16.30 ± 3.19 and 15.65 ± 3.18 for the pretest, posttest and follow-up posttest, respectively (p value < 0.00). However, the difference between the VP and SP groups was not statistically significant (p = 0.896). Moreover, there was no statistically significant difference between the VP and SP groups regarding the retention of clinical reasoning ability. In terms of learning gain, compared with the VP group, the SP group had a score of 51.46% immediately after clinical reasoning exercise as compared to VP group, in which it was 49.1%. After one month, it was 38.01 in SP and 40.12% in VP group. CONCLUSION: VPs can be used for learning clinical reasoning skills in postgraduate ophthalmology residents in a safe environment. These devices can be used repeatedly without any risk to the real patient. Although similarly useful, SP is limited by its nonavailability for repeated exercises.
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Competência Clínica , Raciocínio Clínico , Internato e Residência , Oftalmologia , Humanos , Oftalmologia/educação , Masculino , Feminino , Adulto , Simulação de Paciente , Paquistão , Educação de Pós-Graduação em Medicina , Avaliação Educacional , Anamnese/normasRESUMO
This study aims to assess the correl ation between t he resilience level of dental students (preclinical and clinical years) and its effects on their academic performance. It is a correlational research study that was carried out on second, third, and final-yea r denta l students at Lahore Medical & Dental College, Lahore. Academic resilience was judged by using the academic resilience scale (ARS-30). The correlation between resilience and academic performance was e s tablished by appl ying the bivar iate Pea rso n correlation. The mean age of the stude nt s was 2 1.49±1.39 years. Among 196 dental students from different years, 132 (67.35%) were females and 64(32.65%) were males. A strong p ositive co rrelati on was obser ved bet ween the academic performance and resilience of denta l students, i.e. r=0.774. From the results, it can be concluded that there is a positive correlation between academic resilience and academic performance among dental students.
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Desempenho Acadêmico , Resiliência Psicológica , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Estudantes de OdontologiaRESUMO
Background & Objective: Emotional intelligence (EI) can become a vital tool for resolving clinical conflicts (CC) in surgery. The postgraduate residents focus on the technical skills and undermine the soft skills required for their better training. Our aim was to determine the EI of postgraduate resident (PGR) years one & two in General and Orthopedic Surgery. The CC in their workplace and how they use their EI to resolve these conflicts. Methods: This mixed-method study was conducted from March 10, 2019 to May 28, 2020 at Departments of General and Orthopedic Surgery, Mayo Hospital, Lahore. The study was conducted in two phases 1 & 2. In Phase-1, one hundred PGR years one & two were administered the Mayor-Salovey-Caruso Emotional Intelligence test (MSCEIT) to measure EI. In phase-2, semi-structured in-depth interviews of 10 PGRs five with high and five with low EI were conducted to determine the CC and use of EI to resolve the CC at the workplace. A thematic analysis was done. Results: Out of 100 PGR, the mean EI score was 46.25±14.8 with a maximum score of 75.4, and a minimum score of 18.16 (p-value =0.775). Ninety-one (91%) have not improving EI, and 09 (09%) have considered developing EI. Five themes in four settings, including emergency, ward, elective operation theatre, and outpatient department (OPD) were determined. The emerged themes for the CC were nepotism, gender biases, burnout, lack of professionalism, and toxic culture. The following were CC management strategies: self-study, deceit, gender affinity, performing attention-attaining work, aggrieved reaction and being disgruntled when alone. Conclusion: None of the PGR was emotionally intelligent in overall grades, as well as a particular aspect of MSCEIT.
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Objective: To develop an instrument to identify the challenges faced by faculty while implementing an integrated curriculum in an undergraduate dentistry program. Methods: The study was conducted between September 2020 and October 2021 at the University College of Medicine and Dentistry (UCMD), University of Lahore (UOL). A preliminary questionnaire, developed through literature review and faculty interviews was sent to 10 medical education experts for content validation via the Delphi technique. Content Validity Index (CVI) was calculated for individual items (I-CVI) as well as for the composite scale (S-CVI). A panel agreement of more than 75% was considered as the criterion for the inclusion of items in the questionnaire. Cognitive pretesting of five faculty members was conducted and pilot testing was subsequently done with 27 faculty members. The reliability of the tool was determined by Cronbach's alpha. Results: After the Delphi process, the final Integrated Curriculum Implementation Challenges (ICIC) questionnaire had 42 items. S-CVI was 0.87 and the cut-off value for I-CVI was taken as 0.78 as the criterion for item deletion. Cognitive interviews and pretesting revealed good item interpretation. Cronbach's alpha for this tool was 0.87. Conclusion: ICIC is a useful instrument with good reliability and content validity. It can be used to identify the presence and extent of challenges faced by the faculty while implementing an integrated curriculum.
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Cancer has complex pathophysiology and is one of the primary causes of death and morbidity across the world. Chemotherapy, targeted therapy, radiation therapy, and immunotherapy are examples of traditional cancer treatments. However, these conventional treatment regimens have many drawbacks, such as lack of selectivity, non-targeted cytotoxicity, insufficient drug delivery at tumor sites, and multi-drug resistance, leading to less potent/ineffective cancer treatment. Due to its immanent biophysical property and ability to change in numerous ways, nano-technology has completely transformed how cancer is identified and treated in recent years. Furthermore, nanotechnology providing solutions to these restrictions and boosting cancer therapy. Nanoparticles are widely used nanomedicine platform in cancer immunotherapy due to their excellent physicochemical properties that include size, shape, and surface features, resulting into desirable biological interactions and have been categorized into several types. Nanoparticles can also be potentially be up taken by antigen-presenting cells that promote the cytosolic delivery of encapsulated antigens and adjuvants. Furthermore, nanoparticles can be fine-tuned and functionalized with specific moieties to promote their efficacy in targeting and delivering cargo materials to specific locations. In this review, we summarized and discussed nanoparticles and potential features to be used as carriers in cancer immunotherapy, the current status of different types of nanoparticles, and the importance of their functionalization. Furthermore, we have also discussed nanoparticles-based nanomedicine in targeted delivery of encapsulated cancer immunotherapeutic and their involvement in the modulation of the tumor microenvironment, promoting cancer immunotherapy.
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Nanopartículas , Neoplasias , Humanos , Nanomedicina/métodos , Imunoterapia/métodos , Nanopartículas/química , Microambiente Tumoral , Neoplasias/tratamento farmacológicoRESUMO
Seeman's pioneer idea has led to the foundation of DNA nanostructures, resulting in a remarkable advancement in DNA nanotechnology. Over the last few decades, remarkable advances in drug delivery techniques have resulted in the self-assembly of DNA for encapsulating candidate drug molecules. The nuclear targeting capability of DNA nanostructures is lies within their high spatial addressability and tremendous potential for active targeting. However, effective programming and assembling those DNA molecules remains a challenge, making the path to DNA nanostructures for real-world applications difficult. Because of their small size, most nanostructures are self-capable of infiltrating into the tumor cellular environment. Furthermore, to enable controlled and site-specific delivery of encapsulated drug molecules, DNA nanostructures are functionalized with special moieties that allow them to bind specific targets and release cargo only at targeted sites rather than non-specific sites, resulting in the prevention/limitation of cellular toxicity. In light of this, the current review seeks to shed light on the versatility of the DNA molecule as a targeting and encapsulating moiety for active drugs in order to achieve controlled and specific drug release with spatial and temporal precision. Furthermore, this review focused on the challenges associated with the construction of DNA nanostructures as well as the most recent advances in the functionalization of DNA nanostructures using various materials for controlled and targeted delivery of medications for cancer therapy.
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Nanoestruturas , Neoplasias , Humanos , Nanoestruturas/química , Nanoestruturas/uso terapêutico , DNA , Nanotecnologia/métodos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológicoRESUMO
Ulcerative colitis is a multifactorial disease of the gastrointestinal tract which is caused due to chronic inflammation in the colon; it usually starts from the lower end of the colon and may spread to other portions of the large intestine, if left unmanaged. Budesonide (BUD) is a synthetically available second-generation corticosteroidal drug with potent local anti-inflammatory activity. The pharmacokinetic properties, such as extensive first-pass metabolism and quite limited bioavailability, reduce its therapeutic efficacy. To overcome the limitations, nanosized micelles were developed in this study by conjugating stearic acid with caffeic acid to make an amphiphilic compound. The aim of the present study was to evaluate the pharmacological potential of BUD-loaded micelles in a mouse model of dextran sulfate sodium-induced colitis. Micelles were formulated by the solvent evaporation method, and their physicochemical characterizations show their spherical shape under microscopic techniques like atomic force microscopy, transmission electron microscopy, and scanning electron microscopy. The in vitro release experiment shows sustained release behavior in physiological media. These micelles show cytocompatible behavior against hTERT-BJ cells up to 500 µg/mL dose, evidenced by more than 85% viable cells. BUD-loaded micelles successfully normalized the disease activity index and physical observation of colon length. The treatment with BUD-loaded micelles alleviates the colitis severity as analyzed in histopathology and efficiently, overcoming the disease severity via downregulation of various related cytokines (MPO, NO, and TNF-α) and inflammatory enzymes such as COX-2 and iNOS. Results of the study suggest that BUD-loaded nano-sized micelles effectively attenuate the disease conditions in colitis.
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Colite Ulcerativa , Colite , Camundongos , Animais , Budesonida/farmacologia , Budesonida/uso terapêutico , Micelas , Inflamação/metabolismo , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/tratamento farmacológico , Colo , Modelos Animais de DoençasRESUMO
The development of luminescent dyes based on 1,1,4,4-tetracyanobuta-1,3-dienes (TCBDs) is an active research area, and a quantum yield (ΦF) of 7.8% has been achieved so far in cyclohexane by appending a fluorophore. Our novel method radically refines weakly emissive 2,3-disubstituted TCBD (phenyl-TCBD 1) (ΦF = 2.3% in CH3CN) into a water-soluble, biocompatible nanoformulation as highly emissive aggregates 1NPs â PF-127 with ΦF = 7.9% in H2O and without fluorophore conjugation. Characterization of 1NPs â PF-127 was carried out using various spectroscopic techniques, and its predominant size was found to be 80-100 nm according to transmission electron microscopy and dynamic light scattering techniques. Spectroscopic studies including Fourier transform infrared spectroscopy revealed that aggregated phenyl-TCBD particles were encapsulated in a nonluminescent triblock copolymer (PF-127)-based nanomicelles with the TCBD entrapment efficiency of 77%. With increasing water fraction, the phenyl-TCBD nanoaggregates exhibited a 3-fold higher quantum yield, a greater lifetime, and a red shift (155 nm). This remarkable enhancement in red emissivity enabled them to be used as a bioprobe for bioimaging applications and in photodynamic therapy to selectively target cancer cell lines with singlet oxygen generation capability (ΦΔ = 0.25). According to the MTT assay, compared to the native molecular form (1229 nM), the aggregated 1NPs â PF-127 (13.51 nM) exhibited dose-dependent cell death when exposed to light with 91-fold increased activity. The histoarchitectures of various vital organs (liver, kidneys, heart, lungs, and spleen) were intact when tested for in vivo biocompatibility. This study has significant implications for developing nonplanar push-pull chromophore-based dyes as biosensors and with potential applications beyond bioimaging.
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Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Linhagem Celular , Corantes Fluorescentes/química , Água , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/químicaRESUMO
BACKGROUND: It is currently under discussion whether Learner Handovers (LH) are beneficial, disadvantageous, or useful in Health Professions Education. Research has not been conducted to determine the extent of existing informal learner handover (ILH) through faculty discussions. In addition to providing stakeholders with added context, examining the nature of ILH may also provide insight into the bias associated with Learner Handover. METHODS: Transcripts from a series of semi-structured Focus Group Discussions (FGDs) and interviews (from January to March 2022) were iteratively reviewed to identify relevant patterns and correlations. The study involved the voluntary participation of 16 active clinical dental faculty members with a variety of designations. We did not discard any opinions. RESULTS: It was found that ILH had a mild impact on students' training. ILH effects can be categorized into four key areas: (1) faculty behavior with students, (2) faculty expectations from students, 3) teaching approach, and 4) faculty feedback practices. Furthermore, five additional factors were identified as having a greater influence on ILH practices. CONCLUSIONS: In clinical dental training, ILH has a minor effect on faculty-student interactions. Faculty perceptions and ILH are strongly influenced by other factors contributing to the student's 'academic reputation. As a result, student-faculty interactions are never free of prior influences, so stakeholders need to take them into consideration when creating a formal LH.
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Docentes de Enfermagem , Estudantes , Humanos , Grupos Focais , Retroalimentação , Educação em OdontologiaRESUMO
BACKGROUND: There are multiple instruments to measure different learning environments but no valid and reliable instrument is present for measuring the micro-learning environment. This study aimed to develop and validate an instrument to measure the micro-learning environment of students. Measuring the micro-learning environment can give insight into the real-life experiences of students and enlighten us about the disparity between taught, delivered, and learned curricula. METHODS: Multi-institutional Mixed methods study design with consecutive qualitative and, quantitative components was used based on information processing theory. Literature review, results of semi-structured interviews, and focus group discussion were combined to develop a questionnaire. Content and response process validity were established followed by pilot testing, reliability calculation, and exploratory and confirmatory factor analysis. RESULTS: A forty-nine-item preliminary draft instrument was reduced to a total of twenty-four items final instrument having five themes regarding teaching practices, learners support, competence in teaching, progressive faculty, and teaching environment. The values of SCVI/Ave and S-CVI/UA were calculated to be 0.92 and 0.62 respectively. Reliability was calculated to be 0.94. Fit indices values were within the normal range. CONCLUSION: The instrument for measuring the micro-learning environment has excellent content, construct, response process validity, and reliability.
Assuntos
Aprendizagem , Estudantes de Enfermagem , Humanos , Avaliação Educacional/métodos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
PURPOSE: The primary objective of our study is twofold. First, we assessed nontechnical skills (NTSs), such as the cognitive, social, and personal skills of postgraduate residents (PGRs), from paediatric caregivers' perspectives in a paediatric emergency department (PED) of a tertiary care hospital. Second, we evaluated the reliability and validity of the 'Parents' Assessment of Residents Enacting Non-Technical Skills' (PARENTS) instrument in its Urdu-translated version, ensuring its applicability and accuracy in the Pakistani context. MATERIALS AND METHODS: This mixed-method study used an instrument translation and validation design. We translated an existing instrument, PARENTS, into Urdu, the national language of Pakistan, and administered it to paediatric caregivers in the PED of a tertiary care hospital. We collected data from 471 paediatric caregivers and coded them for analysis in AMOS and SPSS. RESULTS: The Urdu-translated version of the PARENTS demonstrated reliability and internal validity in our study. The findings from the assessment revealed that paediatric caregivers expressed satisfaction with the knowledge and skill of residents. However, there was comparatively lower satisfaction regarding the residents' display of patience or empathy towards the children under their care. CONCLUSION: The study findings support the validity and reliability of the PARENTS as an effective instrument for assessing the NTS of PGRs from the perspective of paediatric caregivers. With its demonstrated efficacy, medical educators can utilize PARENTS to pinpoint specific areas that require attention regarding the NTS of PGRs, thus facilitating targeted interventions for enhanced patient care outcomes.