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1.
BMC Public Health ; 24(1): 1280, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730455

RESUMO

INTRODUCTION: The increasing ageing of the population with growth in NCD burden in India has put unprecedented pressure on India's health care systems. Shortage of skilled human resources in health, particularly of specialists equipped to treat NCDs, is one of the major challenges faced in India. Keeping in view the shortage of healthcare professionals and the guidelines in NEP 2020, there is an urgent need for more health professionals who have received training in the diagnosis, prevention, and treatment of NCDs. This paper conducts a scoping review and aims to collate the existing evidence on the use of digital education of health professionals within NCD topics. METHODS: We searched four databases (Web of Science, PubMed, EBSCO Education Research Complete, and PsycINFO) using a three-element search string with terms related to digital education, health professions, and terms related to NCD. The inclusion criteria covered the studies to be empirical and NCD-related with the target population as health professionals rather than patients. Data was extracted from 28 included studies that reported on empirical research into digital education related to non-communicable diseases in health professionals in India. Data were analysed thematically. RESULTS: The target groups were mostly in-service health professionals, but a considerable number of studies also included pre-service students of medicine (n = 6) and nursing (n = 6). The majority of the studies included imparted online learning as self-study, while some imparted blended learning and online learning with the instructor. While a majority of the studies included were experimental or observational, randomized control trials and evaluations were also part of our study. DISCUSSION: Digital HPE related to NCDs has proven to be beneficial for learners, and simultaneously, offers an effective way to bypass geographical barriers. Despite these positive attributes, digital HPE faces many challenges for its successful implementation in the Indian context. Owing to the multi-lingual and diverse health professional ecosystem in India, there is a need for strong evidence and guidelines based on prior research in the Indian context.


Assuntos
Pessoal de Saúde , Doenças não Transmissíveis , Humanos , Doenças não Transmissíveis/prevenção & controle , Doenças não Transmissíveis/terapia , Índia , Pessoal de Saúde/educação , Educação a Distância
2.
Surg Endosc ; 38(4): 2010-2018, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38413471

RESUMO

BACKGROUND: To investigate factors associated with risk for rebleeding and 30-day mortality following prophylactic transarterial embolization in patients with high-risk peptic ulcer bleeding. METHODS: We retrospectively reviewed medical records and included all patients who had undergone prophylactic embolization of the gastroduodenal artery at Rigshospitalet, Denmark, following an endoscopy-verified and treated peptic Sulcer bleeding, from 2016 to 2021. Data were collected from electronic health records and imaging from the embolization procedures. Primary outcomes were rebleeding and 30-day mortality. We performed logistical regression analyses for both outcomes with possible risk factors. Risk factors included: active bleeding; visible hemoclips; Rockall-score; anatomical variants; standardized embolization procedure; and number of endoscopies prior to embolization. RESULTS: We included 176 patients. Rebleeding occurred in 25% following embolization and 30-day mortality was 15%. Not undergoing a standardized embolization procedure increased the odds of both rebleeding (odds ratio 3.029, 95% confidence interval (CI) 1.395-6.579) and 30-day overall mortality by 3.262 (1.252-8.497). More than one endoscopy was associated with increased odds of rebleeding (odds ratio 2.369, 95% CI 1.088-5.158). High Rockall-score increased the odds of 30-day mortality (odds ratio 2.587, 95% CI 1.243-5.386). Active bleeding, visible hemoclips, and anatomical variants did not affect risk of rebleeding or 30-day mortality. Reasons for deviation from standard embolization procedure were anatomical variations, targeted treatment without embolizing the gastroduodenal artery, and technical failure. CONCLUSIONS: Deviation from the standard embolization procedure increased the risk of rebleeding and 30-day mortality, more than one endoscopy prior to embolization was associated with higher odds of rebleeding, and a high Rockall-score increased the risk of 30-day mortality. We suggest that patients with these risk factors are monitored closely following embolization. Early detection of rebleeding may allow for proper and early re-intervention.


Assuntos
Hemostase Endoscópica , Úlcera Péptica , Humanos , Estudos Retrospectivos , Hemostase Endoscópica/métodos , Fatores de Risco , Úlcera Péptica Hemorrágica/etiologia , Úlcera Péptica Hemorrágica/terapia , Úlcera Péptica/terapia , Recidiva
3.
NPJ Precis Oncol ; 8(1): 53, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413842

RESUMO

Epithelial ovarian cancer (EOC) is the gynaecological malignancy with highest mortality. Although adjuvant treatment with carboplatin and paclitaxel leads to an objective response in ~80% of these patients, a majority will relapse within two years. Better methods for assessing long-term treatment outcomes are needed. To address this, we established safe and efficacious doses of carboplatin and paclitaxel using IGROV-1 zebrafish-CDX models. Then fluorescently-labelled cell suspensions from 83 tumour biopsies collected at exploratory laparotomy of women with suspected EOC were generated and 37 (45%) were successfully implanted in zebrafish larvae. Among these 19 of 27 pathology-confirmed EOC samples (70%) engrafted. These zebrafish patient-derived tumour xenograft (ZTX) models were treated with carboplatin or paclitaxel and tumour growth/regression and metastatic dissemination were recorded. In a subgroup of nine patients, four ZTX models regressed during carboplatin treatment. All four corresponding patients had >24 months PFS. Furthermore, both ZTX models established from two patients having <24 months PFS failed to regress during carboplatin treatment. Seven of eight models seeding <6 metastatic cells were established from patients having >24 months PFS. In eleven of fourteen patients, FIGO stage I + II or III tumours gave rise to ZTX models seeding <4 or >4 metastatic cells, respectively. In conclusion, ZTX models predicted patients having >24 or <24 months PFS, based on response/no response to carboplatin. Furthermore, high metastatic dissemination in ZTX models correlated to shorter PFS and more advanced disease at diagnosis. These preliminary results suggest that ZTX models could become a useful prognostic tool in EOC treatment planning.

4.
J Neurooncol ; 166(3): 503-511, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38336917

RESUMO

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.


Assuntos
Neoplasias Meníngeas , Meningioma , Humanos , Idoso , Meningioma/patologia , Neoplasias Meníngeas/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Medição de Risco
5.
Cancer Cell Int ; 24(1): 75, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38355625

RESUMO

PURPOSE: To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients. MATERIALS AND METHODS: The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry. Gene expression analysis and pathway analysis were conducted using RNA-seq data. RESULTS: All cancer lines tested, including SW480, SW480-KO13 (RhoB knockout), SW480-KO55 (RhoB knockout), HCT116 and HCT116-OE (RhoB overexpressed), exhibited cytotoxicity to 5-FU and OXL. RhoB knockout cell lines demonstrated significantly reduced migration compared to the control cell lines. Furthermore, RhoB played a role in caspase-3-dependent apoptosis, regulation of ROS production and autophagic flux. The mRNA sequencing data indicated lower expression levels of oncogenes in RhoB knockout cell lines. The zebrafish model bearing SW480-KO showed a light trend toward tumor regression. RhoB expression by immunohistochemistry in patients was increased from normal mucosa to tumor samples. In patients who received chemotherapy, high RhoB expression was related to worse survival compared to low RhoB expression. Furthermore, the molecular docking analysis revealed that OXL had a higher binding affinity for RhoB than 5-FU, with a binding affinity of -7.8 kcal/mol and HADDOCK predicted molecular interactions between RhoB and caspase 3 protein. Gene-set enrichment analysis supported these findings, showing that enrichment of DNA damage response pathway and p53 signaling in RhoB overexpression treatment group, while the RhoB knockout treatment group exhibited enrichment in the negative regulation pathway of cell migration. CONCLUSION: RhoB was negatively associated with chemotherapy response and survival in colorectal cancers. Therefore, RhoB inhibition may enhance chemotherapeutic responses and patient survival.

6.
Eur J Orthop Surg Traumatol ; 34(3): 1479-1486, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38253932

RESUMO

PURPOSE: The Focused Assessment with Sonography for Trauma (FAST) is a tool to rapidly detect intraabdominal and intrapericardial fluid with point-of-care ultrasound. Previous studies have questioned the role of FAST in patients with pelvic fractures. The aim of the present study was to assess the accuracy of FAST to detect clinically significant intraabdominal hemorrhage in patients with pelvic fractures. METHODS: We included all consecutive patients with pelvic and/or acetabular fractures treated our Level 1 trauma center from 2009-2020. We registered patient and fracture characteristics, FAST investigations and CT descriptions, explorative laparotomy findings, and transfusion needs. We compared FAST to CT and laparotomy findings, and calculated true positive and negative findings, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: We included 389 patients. FAST had a sensitivity of 75%, a specificity of 98%, a PPV of 84%, and a NPV of 96% for clinically significant intraabdominal bleeding. Patients with retroperitoneal hematomas were at increased risk for laparotomy both because of True-negative FAST and False-positive FAST. CONCLUSION: FAST is accurate to identify clinically significant intraabdominal blood in patients with severe pelvic fractures and should be a standard asset in these patients. Retroperitoneal hematomas challenge the FAST interpretation and thus the decision making when applying FAST in patients with pelvic fractures.


Assuntos
Fraturas Ósseas , Fraturas do Quadril , Ossos Pélvicos , Fraturas da Coluna Vertebral , Ferimentos não Penetrantes , Humanos , Fraturas Ósseas/complicações , Fraturas Ósseas/diagnóstico por imagem , Hematoma/complicações , Hemoperitônio/etiologia , Fraturas do Quadril/complicações , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/lesões , Estudos Retrospectivos , Sensibilidade e Especificidade , Fraturas da Coluna Vertebral/complicações , Ferimentos não Penetrantes/complicações
7.
J Chem Phys ; 160(2)2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38214392

RESUMO

For large plasmonic nanoparticles, retardation effects become important once their length becomes comparable to the wavelength of light. However, most models do not incorporate retardation effects due to the high computational cost of solving for the optical properties of large atomistic electrodynamics systems. In this work, we derive and implement a recursive fast multipole method (FMM) in Cartesian coordinates that includes retardation effects. In this method, higher-order electrodynamic interaction tensors used for the FMM are calculated recursively, thus greatly reducing the implementation complexity of the model. This method allows for solving of the optical properties of large atomistic nanoparticles with controlled accuracy; in practice, taking the expansion to the fifth order provides a good balance of accuracy and computational time. Finally, we study the effects retardation has on the near- and far-field properties of large plasmonic nanoparticles with over a million atoms using this method. We specifically focus on nanorods and their dimers, which are known to generate highly confined fields in their junctions. In the future, this method can be applied to simulations in which accurate near-field properties are required, such as surface-enhanced Raman scattering.

8.
J Chem Phys ; 160(1)2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38174789

RESUMO

Strong light-matter interactions significantly modify the optical properties of molecules in the vicinity of plasmonic metal nanoparticles. Since the dimension of the plasmonic cavity approaches that of the molecules, it is critical to explicitly describe the nanoparticle junctions. In this work, we use the discrete interaction model/quantum mechanical (DIM/QM) method to model the coupling between the plasmonic near-field and molecular excited states. DIM/QM is a combined electrodynamics/quantum mechanical model that uses an atomistic description of the nanoparticle. We extend the DIM/QM method to include the local field effects in the sum-over-state formalism of time-dependent density functional theory. As a test of the method, we study the interactions between small organic chromophores and metal nanoparticles. In particular, we examine how the inclusion of multiple electronic transitions and intermolecular interactions modify the coupling between molecules and nanoparticles. Using the sum-over-state formalism of DIM/QM, we show that two-state models break down when the plasmon excitation is detuned from the molecular excitations. To gain further insight, we compare the simple coupled-dipole model (CDM) with the DIM/QM model. We find that CDM works well for simple systems but fails when going beyond the single molecule or single nanoparticle cases. We also find that the coupling depends strongly on the site of the nanoparticle in which the chromophore couples to. Our work suggests the importance of explicitly describing the cavity to capture the atomistic level local field environment in which the molecule strongly couples to.

9.
J Chem Theory Comput ; 20(2): 937-945, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38164716

RESUMO

DNA-stabilized silver nanoclusters have emerged as an intriguing type of nanomaterial due to their unique optical and electronic properties, with potential applications in areas such as biosensing and imaging. The development of efficient methods for modeling these properties is paramount for furthering the understanding and utilization of these clusters. In this study, a hybrid quantum mechanical and molecular mechanical approach for modeling the optical properties of a DNA-templated silver nanocluster is evaluated. The influence of different parameters, including ligand fragmentation, damping, embedding potential, basis set, and density functional, is investigated. The results demonstrate that the most important parameter is the type of atomic properties used to represent the ligands, with isotropic dipole-dipole polarizabilities outperforming the rest. This underscores the importance of an appropriate representation of the ligands, particularly through the selection of the properties used to represent them. Moreover, the results are compared to experimental data, showing that the applied methodology is reliable and effective for the modeling of DNA-stabilized silver nanoclusters. These findings offer valuable insights that may guide future computational efforts to explore and harness the potential of these novel systems.


Assuntos
DNA , Prata , Simulação de Dinâmica Molecular
10.
Biochim Biophys Acta Mol Basis Dis ; 1870(2): 166963, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37989423

RESUMO

Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy affecting the photoreceptors, retinal pigment epithelium (RPE) and choroid, however, the involvement of the choroid in disease progression is not fully understood. CHM is caused by mutations in the CHM gene, encoding the ubiquitously expressed Rab escort protein 1 (REP1). REP1 plays an important role in intracellular trafficking of vesicles, including melanosomes. In this study, we examined the ultrastructure of the choroid in chmru848 fish and Chmnull/WT mouse models using transmission electron and confocal microscopy. Significant pigmentary disruptions were observed, with lack of melanosomes in the choroid of chmru848 fish from 4 days post fertilisation (4dpf), and a reduction in choroidal blood vessel diameter and interstitial pillars suggesting a defect in vasculogenesis. Total melanin and expression of melanogenesis genes tyr, tryp1a, mitf, dct and pmel were also reduced from 4dpf. In Chmnull/WT mice, choroidal melanosomes were significantly smaller at 1 month, with reduced eumelanin at 1 year. The choroid in CHM patients were also examined using spectral domain optical coherence tomography (SD-OCT) and OCT-angiography (OCT-A) and the area of preserved choriocapillaris (CC) was found to be smaller than that of overlying photoreceptors, suggesting that the choroid is degenerating at a faster rate. Histopathology of an enucleated eye from a 74-year-old CHM male patient revealed isolated areas of RPE but no associated underlying CC. Pigmentary disruptions in CHM animal models reveal an important role for REP1 in melanogenesis, and drugs that improve melanin production represent a potential novel therapeutic avenue.


Assuntos
Coroideremia , Idoso , Animais , Humanos , Masculino , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Corioide/metabolismo , Coroideremia/genética , Coroideremia/patologia , Coroideremia/terapia , Melaninas , Melanogênese , Camundongos Knockout
11.
Chem Commun (Camb) ; 59(98): 14524-14527, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-37966800

RESUMO

Gold nanoparticles were functionalized with natural abundance and 13C-labeled N-heterocyclic carbenes (NHCs) to investigate the Au-C stretch. A combinatorial approach of surface enhanced Raman spectroscopy (SERS) and density-functional theory (DFT) calculations highlighted vibrational modes significantly impacted by isotopic labeling at the carbene carbon. Critically, no isotopically-impacted stretching mode showed majority Au-C character.

12.
Open Res Eur ; 3: 88, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37981907

RESUMO

Background: Uveal melanoma is a poor prognosis cancer. Ergolide, a sesquiterpene lactone isolated from Inula Brittanica, exerts anti-cancer properties. The objective of this study was to 1) evaluate whether ergolide reduced metastatic uveal melanoma (MUM) cell survival/viability in vitro and in vivo; and 2) to understand the molecular mechanism of ergolide action. Methods: Ergolide bioactivity was screened via long-term proliferation assay in UM/MUM cells and in zebrafish MUM xenograft models. Mass spectrometry profiled proteins modulated by ergolide within whole cell or extracellular vesicle (EVs) lysates of the OMM2.5 MUM cell line. Protein expression was analyzed by immunoblots and correlation analyses to UM patient survival used The Cancer Genome Atlas (TCGA) data. Results: Ergolide treatment resulted in significant, dose-dependent reductions (48.5 to 99.9%; p<0.0001) in OMM2.5 cell survival in vitro and of normalized primary zebrafish xenograft fluorescence (56%; p<0.0001) in vivo, compared to vehicle controls. Proteome-profiling of ergolide-treated OMM2.5 cells, identified 5023 proteins, with 52 and 55 proteins significantly altered at 4 and 24 hours, respectively ( p<0.05; fold-change >1.2). Immunoblotting of heme oxygenase 1 (HMOX1) and growth/differentiation factor 15 (GDF15) corroborated the proteomic data. Additional proteomics of EVs isolated from OMM2.5 cells treated with ergolide, detected 2931 proteins. There was a large overlap with EV proteins annotated within the Vesiclepedia compendium. Within the differentially expressed proteins, the proteasomal pathway was primarily altered. Interestingly, BRCA2 and CDKN1A Interacting Protein (BCCIP) and Chitinase Domain Containing 1 (CHID1), were the only proteins significantly differentially expressed by ergolide in both the OMM2.5 cellular and EV isolates and they displayed inverse differential expression in the cells versus the EVs. Conclusions: Ergolide is a novel, promising anti-proliferative agent for UM/MUM. Proteomic profiling of OMM2.5 cellular/EV lysates identified candidate pathways elucidating the action of ergolide and putative biomarkers of UM, that require further examination.


The most common form of adult eye cancer is uveal melanoma (UM). Once UM cancer cells spread to organs in the rest of the body, metastatic UM (MUM), there is a poor prognosis for patients with only one approved drug treatment. Hence, it is vital to better understand the cellular and extracellular proteins that regulate UM pathology in order to uncover biomarkers of disease and therapeutic targets. In this original study, we demonstrate a compound called ergolide is capable of severely reducing the metabolic activity and growth of UM cancer cells, grown as isolated monolayers. Ergolide was also able to reduce the growth of human MUM cells growing as tumors in transplanted zebrafish larvae. We identify that ergolide alters specific proteins found in the human UM cells. These proteins once analyzed in detail offer opportunities to understand how new treatment strategies can be developed for UM.

14.
Adv Drug Deliv Rev ; 201: 115084, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37689278

RESUMO

Ocular surface neovascularization and its resulting pathological changes significantly alter corneal refraction and obstruct the light path to the retina, and hence is a major cause of vision loss. Various factors such as infection, irritation, trauma, dry eye, and ocular surface surgery trigger neovascularization via angiogenesis and lymphangiogenesis dependent on VEGF-related and alternative mechanisms. Recent advances in antiangiogenic drugs, nanotechnology, gene therapy, surgical equipment and techniques, animal models, and drug delivery strategies have provided a range of novel therapeutic options for the treatment of ocular surface neovascularization. In this review article, we comprehensively discuss the etiology and mechanisms of corneal neovascularization and other types of ocular surface neovascularization, as well as emerging animal models and drug delivery strategies that facilitate its management.


Assuntos
Neovascularização da Córnea , Medicina Molecular , Animais , Neovascularização Patológica/tratamento farmacológico , Neovascularização da Córnea/tratamento farmacológico , Neovascularização da Córnea/patologia , Retina/patologia , Inibidores da Angiogênese/uso terapêutico
16.
Signal Transduct Target Ther ; 8(1): 305, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37591843

RESUMO

Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.


Assuntos
Fator 2 de Crescimento de Fibroblastos , Fator B de Crescimento do Endotélio Vascular , Humanos , Fator 2 de Crescimento de Fibroblastos/genética , Imunoterapia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética
17.
BMC Med Educ ; 23(1): 561, 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37559028

RESUMO

BACKGROUND: The World Health Organization (WHO) predicts a global shortfall of 18 million health workers by 2030, particularly in low- and middle-income countries like India. The country faces challenges such as inadequate numbers of health professionals, poor quality of personnel, and outdated teaching styles. Digital education may address some of these issues, but there is limited research on what approaches work best in the Indian context. This paper conducts a scoping review of published empirical research related to digital health professions education in India to understand strengths, weaknesses, gaps, and future research opportunities. METHODS: We searched four databases using a three-element search string with terms related to digital education, health professions, and India. Data was extracted from 36 included studies that reported on empirical research into digital educational innovations in the formal health professions education system of India. Data were analysed thematically. RESULTS: Most study rationales related to challenges facing the Indian health care system, rather than a wish to better understand phenomena related to teaching and learning. Similarly, most studies can be described as general evaluations of digital educational innovations, rather than educational research per se. They mostly explored questions related to student perception and intervention effectiveness, typically in the form of quantitative analysis of survey data or pre- and post-test results. CONCLUSIONS: The analysis revealed valuable insights into India-specific needs and challenges. The Indian health professions education system's size and unique challenges present opportunities for more nuanced, context-specific investigations and contributions to the wider digital education field. This, however, would require a broadening of methodological approaches, in particular rigorous qualitative designs, and a focus on addressing research-worthy educational phenomena.


Assuntos
Ocupações em Saúde , Pessoal de Saúde , Humanos , Pessoal de Saúde/educação , Aprendizagem , Educação em Saúde/métodos , Escolaridade
18.
J Phys Chem Lett ; 14(25): 5727-5733, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37318362

RESUMO

This presentation considers the effects that DNA-templating has on the optical properties of a 16-atom silver cluster. To accomplish this, hybrid quantum mechanical and molecular mechanical simulations of a Ag16-DNA complex have been carried out and compared with pure time-dependent density functional theory calculations of two Ag16 clusters in vacuum. The presented results show that the templating DNA polymers both red-shift the one-photon absorption of the silver cluster and increase its intensity. This occurs through a change in cluster shape prompted by the structural constraints of the DNA ligands combined with silver-DNA interactions. The overall charge of the cluster also contributes to the observed optical response, as oxidation of the cluster results in a simultaneous blue-shift of the one-photon absorption and a decrease in intensity. Additionally, the changes in shape and environment also lead to a blue-shift and enhancement of the two-photon absorption.


Assuntos
DNA , Prata , Prata/química , DNA/química , Teoria da Densidade Funcional
19.
Adv Sci (Weinh) ; 10(24): e2301505, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37330661

RESUMO

The circadian clock in animals and humans plays crucial roles in multiple physiological processes. Disruption of circadian homeostasis causes detrimental effects. Here, it is demonstrated that the disruption of the circadian rhythm by genetic deletion of mouse brain and muscle ARNT-like 1 (Bmal1) gene, coding for the key clock transcription factor, augments an exacerbated fibrotic phenotype in various tumors. Accretion of cancer-associated fibroblasts (CAFs), especially the alpha smooth muscle actin positive myoCAFs, accelerates tumor growth rates and metastatic potentials. Mechanistically, deletion of Bmal1 abrogates expression of its transcriptionally targeted plasminogen activator inhibitor-1 (PAI-1). Consequently, decreased levels of PAI-1 in the tumor microenvironment instigate plasmin activation through upregulation of tissue plasminogen activator and urokinase plasminogen activator. The activated plasmin converts latent TGF-ß into its activated form, which potently induces tumor fibrosis and the transition of CAFs into myoCAFs, the latter promoting cancer metastasis. Pharmacological inhibition of the TGF-ß signaling largely ablates the metastatic potentials of colorectal cancer, pancreatic ductal adenocarcinoma, and hepatocellular carcinoma. Together, these data provide novel mechanistic insights into disruption of the circadian clock in tumor growth and metastasis. It is reasonably speculated that normalization of the circadian rhythm in patients provides a novel paradigm for cancer therapy.


Assuntos
Neoplasias Hepáticas , Fator de Crescimento Transformador beta , Camundongos , Humanos , Animais , Fator de Crescimento Transformador beta/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Fibrinolisina/metabolismo , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Músculos , Encéfalo/metabolismo , Microambiente Tumoral
20.
Surg Oncol ; 49: 101967, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37356316

RESUMO

PURPOSE: The aim of this study was to evaluate the long-term surgical and oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer during an implementation phase on a national level. METHOD: This is a retrospective review of prospectively recorded data. Registration was initiated by the Danish Colorectal Cancer Group in order to assess the quality of care during the implementation of TaTME in Denmark. Data from four centers were pooled for simultaneous analysis. Short-term data was available from a prior study, and long-term data regarding recurrences, chemotherapy, and mortality was collected. RESULTS: From August 2016 to April 2019, 115 TaTME procedures were registered. Patients were predominantly male (n = 85, 74%) with mid-rectal (n = 88, 77%) tumors. The overall local recurrence rate was 7.8% (n = 9) of which six patients also had systemic recurrence. Mean long-term follow-up was 59.4 months, and median time to local recurrence was 24.9 months. Local recurrences occurred predominantly among initial implementation cases. The overall mortality rate was 13% (n = 15). Of the 17 patients with recurrence, 35% (n = 6) died and developed either solely distant recurrence (n = 2, 12%) or in combination with local recurrence (n = 4, 24%). CONCLUSION: We found acceptable long-term oncological results after TaTME during the implementation phase in Denmark. There was an accumulation of local recurrences in the early phase of the study which emphasizes the importance of thorough training and proctoring when starting the approach.


Assuntos
Laparoscopia , Neoplasias Retais , Cirurgia Endoscópica Transanal , Humanos , Masculino , Feminino , Estudos Prospectivos , Complicações Pós-Operatórias/cirurgia , Cirurgia Endoscópica Transanal/métodos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Dinamarca/epidemiologia , Recidiva , Laparoscopia/métodos , Resultado do Tratamento
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