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Pancreatic ductal adenocarcinoma (PDAC) is one of the most recalcitrant cancers due to its late diagnosis, poor therapeutic response, and highly heterogeneous microenvironment. Nanotechnology has the potential to overcome some of the challenges to improve diagnostics and tumor-specific drug delivery but they have not been plausibly viable in clinical settings. The review focuses on active targeting strategies to enhance pancreatic tumor-specific uptake for nanoparticles. Additionally, this review highlights using actively targeted liposomes, micelles, gold nanoparticles, silica nanoparticles, and iron oxide nanoparticles to improve pancreatic tumor targeting. Active targeting of nanoparticles toward either differentially expressed receptors or PDAC tumor microenvironment (TME) using peptides, antibodies, small molecules, polysaccharides, and hormones has been presented. We focus on microenvironment-based hallmarks of PDAC and the potential for actively targeted nanoparticles to overcome the challenges presented in PDAC. It describes the use of nanoparticles as contrast agents for improved diagnosis and the delivery of chemotherapeutic agents that target various aspects within the TME of PDAC. Additionally, we review emerging nano-contrast agents detected using imaging-based technologies and the role of nanoparticles in energy-based treatments of PDAC. This article is categorized under: Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.
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Nanopartículas , Neoplasias Pancreáticas , Nanomedicina Teranóstica , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Nanopartículas/química , Nanopartículas/uso terapêutico , Microambiente Tumoral , Sistemas de Liberação de Medicamentos , Camundongos , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/diagnóstico por imagemRESUMO
Introduction The COVID-19 pandemic has been a major public health and economic issue worldwide. Even though vaccines have been developed to reduce the spread of the infection, treating patients remains a significant challenge. This study aims to measure the perceptions of Saudis toward participating in the COVID-19 Convalescent Plasma Clinical Trial. Method A cross-sectional study measuring the perceptions of Saudis toward participating in the COVID-19 Convalescent Plasma Clinical Trial was conducted with participants who had recovered from COVID-19. The study used an online questionnaire covering variables related to demographics, awareness, attitudes, perceptions, and plans for improvement. Results A sample of 1,051 participants participated in the questionnaire. A total of 85% had recovered from COVID-19, only 2.76% had participated in clinical trials before, and 83.44% would participate if they were advised or knew about them. The participants showed a high level of education, with 88% having obtained a degree and most used social media. The results can be biased toward the participants who get their knowledge from social media and hope to learn about things on social media. The gap in knowledge about clinical trials among the participants indicated that certain age groups could be targeted through channels where they communicate the most. Conclusion Engaging the community in clinical trials and educating others about their value by sharing experiences would help promote clinical trials and activate donations.
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Jordan has never conducted a nutrition survey to determine nutrient and energy intakes. The current study aimed to describe the energy and macronutrient consumed by the Jordanian population. A cross-sectional food consumption study was conducted, including a sample of Jordanians using two non-consecutive 24-h dietary recalls (24-h DR) between October 2021 and March 2022. A total of 2145 males and females aged 8 to 85 years old living in households were studied. The average of two 24-h DRs for each individual was converted into energy and nutrient intakes. After measuring weight, height, and waist circumference, the body mass index (BMI) and waist-to-height ratio (WHtR) were calculated. The percentage of under-reporters was higher in women than men (58.2% vs. 45.9%). Adults and older adult women had the highest prevalence of obesity (29.6%), while adults and older adult men had the highest prevalence of overweight (41.4%). There is a significant increase in energy intake in children, boys, and all adults, compared to the recommended calories. The mean energy percentage (E %) of total fat was 38%, exceeding the upper limit of the Acceptable Macronutrient Distribution Range (AMDR). At the same time, the mean daily dietary fiber intake fell below the recommended levels (ranging from 13.5 g in children to 19.5 g in older adults). The study population consumes more fat and less fiber than the recommended levels. Actions must be taken across all age groups to correct the deviation of energy and macronutrient intakes from the recommended dietary allowances.
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Dieta , Ingestão de Energia , Masculino , Criança , Humanos , Feminino , Idoso , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Jordânia/epidemiologia , Estudos Transversais , Índice de Massa Corporal , Ingestão de Alimentos , Inquéritos Nutricionais , Gorduras na DietaRESUMO
BACKGROUND: Diagnostic error is a major source of patient suffering. Researchshows that physicians experience frequent interruptions while being engaged with patients and indicate that diagnostic accuracy may be impaired as a result. Since most studies in the field are observational, there is as yet no evidence suggesting a direct causal link between being interrupted and diagnostic error. Theexperiments reported in this article were intended to assess this hypothesis. METHODS: Three experiments were conducted to test the hypothesis that interruptions hurt diagnostic reasoning and increase time on task. In the first experiment (N = 42), internal medicine residents, while diagnosing vignettes of actual clinical cases were interrupted halfway with a task unrelated to medicine, solving word-spotting puzzles and anagrams. In the second experiment (N = 78), the interruptions were medically relevant ones. In the third experiment (N = 30), we put additional time pressure on the participants. In all these experiments, a control group diagnosed the cases without interruption. Dependent variables were diagnostic accuracy and amount of time spent on the vignettes. RESULTS: In none of the experiments interruptions were demonstrated to influence diagnostic accuracy. In Experiment 1: Mean of interrupted group was 0.88 (SD = 0.37) versus non- interrupted group 0.91 (SD = 0.32). In Experiment 2: Mean of interrupted group was 0.95 (SD = 0.32) versus non-interrupted group 0.94 (SD = 0.38). In Experiment 3: Mean of interrupted group was 0.42 (SD = 0.12) versus non-interrupted group 0.37 (SD = 0.08). Although interrupted residents in all experiments needed more time to complete the diagnostic task, only in Experiment 2, this effect was statistically significant. CONCLUSIONS: These three experiments, taken together, failed to demonstrate negative effects of interruptions on diagnostic reasoning. Perhaps physicians who are interrupted may still have sufficient cognitive resources available to recover from it most of the time.
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Médicos , Erros de Diagnóstico , HumanosRESUMO
Background: During pregnancy, the risk of venous thrombo-embolism (VTE) is increased at least five times compared with non-pregnant women of the same age, while the relative risk in the postpartum period can be as high as sixty times. The aim of the study was to explore the impact of pregnancy-related VTE on patients' mental, professional, social and personal life. Methods and Materials: Cross-sectional study at Jordan University Hospital's Obstetrics Department. Results: There were 112 women. Forty-six (41.1%) had a postpartum VTE. Twenty-eight of the patients (25%) had comorbidity. Eleven (9.9%) had a previous episode of VTE. Thirty-nine (35%) of the women reported three or more hospital visits over the past six months. Twenty-one (19.6%) of the women answered that their leg or chest pain has impeded their social activities. Anxiety/Depression was reported by 96.43% while Pain/Discomfort by 73.21%. A significant reduction of time spent on their work (correlation = 0.663, significant at <0.01) and accomplishing less work (correlation = 0.787, this was significant at <0.01) was found; 57.14% of patients indicated that VTE affecting their future pregnancies; 58.9% of patients were receiving anticoagulants with the most commonly used drug was aspirin. Twenty-four (36.4%) of the women were on multiple anticoagulant therapies. Twenty-five of the patients receiving medications do not monitor their medications and 20 patients said that monitoring the drug level was a bother to them. Conclusions: Pregnancy-related VTE had a significant adverse impact on physical, mental and professional life of women. It also had negative effects on future pregnancy plans.
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Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Adulto , Feminino , Humanos , Gravidez , Qualidade de Vida , Fatores de RiscoRESUMO
OBJECTIVE: We aimed to investigate the association of increased smartphone screen time with insomnia, bedtime procrastination, depression, anxiety, body mass index (BMI), and physical activity during the coronavirus disease of 2019 (COVID-19) pandemic. METHODS: An online survey was performed for university students from all regions of Lebanon during the lockdown. The survey included questionnaires about smartphone screen time, diet, physical activity, psychological symptoms, and bedtime procrastination. We defined 6 hours of smartphone use as critical based on a survey done in United States. RESULTS: Among female students, smartphone use duration, physical activity levels, BMI, depression, anxiety, and insomnia severity were significantly higher than in male. When we stratified participants based on 6 hours of smartphone use, females, unhealthy food consumption, insomnia, anxiety, depression, and bedtime procrastination were significantly higher in the group with ≥6 hours of smartphone use. When we divided based on 7 hours, physical activity and body weight also differed between the two groups. Logistic regression analysis revealed that female, overweight, insomnia, and bedtime procrastination were significant predictors of a phone screen time of 7 hours. CONCLUSION: Our findings suggest that adults should be more cautious and responsible when using smartphones and be more concerned about the health-related risks.
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This study explored the psychometric properties of the Arabic version of the Stress and Anxiety to Viral Epidemics-6 items (SAVE-6) scale for assessing people's anxiety in response to the viral epidemic in Lebanon. The 406 participants responded voluntarily to the online survey that included the SAVE-6, Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) tools. The single-structure SAVE-6 model showed good internal consistency (Cronbach's α = 0.773). The SAVE-6 scale also showed good convergent validity with the GAD-7 (Spearman's ρ = 0.42, P < 0.001) and PHQ-9 (ρ = 0.38, P < 0.001). Receiver operating characteristic (ROC) analysis revealed an Arabic SAVE-6 cut-off score of 12 points (area under the curve [AUC] = 0.753; sensitivity = 62.74%; specificity = 78.26%) for an at least mild degree of anxiety (GAD-7 score ≥ 5). The Arabic version of the SAVE-6 was a reliable, valid, and solely usable scale for measuring the anxiety response of the general population to the viral epidemic.
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Transtornos de Ansiedade/epidemiologia , Ansiedade/epidemiologia , COVID-19/psicologia , Pandemias , Escalas de Graduação Psiquiátrica , SARS-CoV-2 , Estresse Psicológico/epidemiologia , Adolescente , Adulto , Idoso , Ansiedade/etiologia , Transtornos de Ansiedade/etiologia , Área Sob a Curva , COVID-19/epidemiologia , Depressão/epidemiologia , Depressão/etiologia , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Autoavaliação Diagnóstica , Análise Fatorial , Feminino , Humanos , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Questionário de Saúde do Paciente , Psicometria , Quarentena/psicologia , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Inquéritos e Questionários , Traduções , Adulto JovemRESUMO
Introduction: Self-efficacy signifies an individual's belief in their own ability to perform the actions required to achieve a particular performance. In this study, we used an online survey to assess the mediation effect of resilience and self-efficacy on the overall psychological well-being of Lebanese people during the crises of the COVID-19 pandemic and the Beirut explosion. Methods: Overall, 567 Lebanese people participated in an online survey between March 17-28, 2021. The survey included the Stress and Anxiety to Viral Epidemics-6 items (SAVE-6), Patient Health Questionnaire-9 (PHQ-9), Connor-Davidson Resilience Scale-2 items, WHO-5 Well-being Index, General Self-Efficacy scale, and a single item on insomnia. We also assessed their risk perception regarding exposure to COVID-19 or explosions. Results: About 53% of participants were assessed as having depression (PHQ-9 ≥ 10) in the recent crisis. About half of participants (53.2%) reported feeling more stressed by COVID-19 than by the Beirut explosion, and 23.4% felt more stressed by the Beirut explosion than by COVID-19. Only the SAVE-6 score differed significantly between groups with greater stress responses to COVID-19 and the Beirut explosion. Self-efficacy mediated the influence of depression on people's psychological well-being, and self-efficacy and resilience mediated the influence of viral anxiety on psychological well-being. Conclusion: Self-efficacy is important for reducing people's depression and improving their psychological well-being during the Lebanon crises and also mediates the influence of anxiety in response to the viral epidemic on their psychological well-being in some people.
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Magnetic manotheranostics can be a fascinating charm to diagnose a tumour with MRI, and treatment through hyperthermia. This study aims to synthesise and characterise magnetically responsive polymer colloids (MRPCs). Healthy tissue damage done by chemotherapy session could be minimised by MRPCs. For the colloidal formulation of MRPCs, the oil in water emulsion technique was employed with the aid of sonication and stirring. The organic phase of emulsion contained methotrexate (MTX) drug, Eudragit E100 and CoFe2O4 (synthesised by co-precipitation) in ethanol, and the aqueous phase contained tween 80 in deionised water. The emulsion was optimised by studying/adjusting two different parameters, i.e. the concentration of constituents and sonication cycles. Multiple formulations were produced at sonication amplitude of 60% at 20 kHz, followed by centrifugation and lyophilisation. Characterisation of MRPCs was done for morphology, size measurement (23-25â nm), surface charge (â¼15.12), coercivity (â¼1549.6â G), magnetisation (2.6 emu) and retentivity (1.34 emu). Drug release in simulating physiological environment (pH = 7.4), was observed for up to 48â h, and, to determine the best release kinetic mechanism results were compared with kinetic models. Magnetic hyperthermia studies showed that MRPCs achieved an acceptable temperature of 42°C, for hyperthermia treatments in cancer patients.
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Cobalto/química , Coloides/química , Composição de Medicamentos/métodos , Compostos Férricos/química , Metotrexato/química , Acrilatos/química , Hipertermia Induzida , Nanopartículas de Magnetita/química , Metotrexato/farmacocinética , Tamanho da Partícula , Polímeros/químicaRESUMO
This study was performed to evaluate the protective efficacy of metoclopramide (MCP) against the organophosphates paraoxon (POX)- and malathion (MLT)-induced apoptosis in the murine L929 skin fibroblasts. L929 cells were exposed to either POX (10 nm) or 1.0 µm MLT in the absence and presence of increased concentrations of MCP. The protective effect of MCP on these organophosphate-stimulated apoptotic events was evaluated by flow cytometry analysis after staining with annexin-V/propidium iodide, processing and activation of the executioner caspase-3, cleavage of the poly-ADP ribose polymerase, fragmentation of the nucleosomal DNA and disruption of the mitochondrial membrane potential (Δψ). Our results showed that increased doses of MCP alone (≥10 µm) did not induce apoptosis or activation of caspase-3. Pretreatment of the cells with MCP attenuated all the apoptotic events triggered by the organophosphate compounds in a dose-dependent manner reaching ~70-80% protection when they were preincubated at 1 and 5 µm of the drug before the addition of POX and MLT, respectively. Interestingly, MCP did not offer a significant protective effect against the cytotoxicity of tumor necrosis factor-α, cisplatinum, etoposide or paclitaxel, which stimulate apoptosis by various mechanisms, suggesting that the anti-apoptotic effect of the drug is specific to organophosphates. The strong and specific anti-apoptotic activity of subclinical doses of MCP against the cytotoxicity of organophosphate compounds suggests its potential clinical application in treating their poisoning.
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Antídotos/farmacologia , Apoptose/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Malation/toxicidade , Metoclopramida/farmacologia , Organofosfonatos/toxicidade , Paraoxon/toxicidade , Pele/efeitos dos fármacos , Animais , Caspase 3/metabolismo , Linhagem Celular , Citoproteção , Relação Dose-Resposta a Droga , Fibroblastos/metabolismo , Fibroblastos/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Poli(ADP-Ribose) Polimerases/metabolismo , Pele/metabolismo , Pele/patologiaRESUMO
The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.
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Doenças Autoimunes/genética , Proteínas de Ligação a DNA/genética , DNA/genética , Proteínas de Membrana/genética , Cromossomos Humanos Par 16 , Humanos , Monócitos/metabolismo , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Locos de Características QuantitativasRESUMO
BACKGROUND: The genetic basis of the autoimmune disease type 1 diabetes (T1D) has now been largely determined, so now we can compare these findings with emerging genetic knowledge of disorders and phenotypes that have been negatively or positively associated with T1D historically. Here, we assessed the role in T1D of variants previously reported to be associated with atopic diseases and epithelial barrier function, profilaggrin (FLG), and those that affect the expression levels of the proinflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, interferon (IFN)γ and IL-18. METHODS: We genotyped single nucleotide polymorphisms (SNPs): -105/rs28665122 in SELS or SEPS1 (selenoprotein), three single nucleotide polymorphisms in IL18 (-105/rs360717, +183/rs5744292 and +1467/rs574456) and R501X/rs61816761 in FLG, the major locus associated with atopic dermatitis and predisposing to asthma, in a minimum of 6743 T1D cases and 7864 controls. RESULTS: No evidence of T1D association was found for any of the SNPs we genotyped at FLG, SELS or IL18 (p≥0.03), nor with haplotypes of IL18 (p=0.82). Review of previous T1D genome-wide association results revealed that four (human leucocyte antigen (HLA), gasdermin B/ORM1 (Saccharomyces cerevisiae)-like/gasdermin B/, GSDMB/ORMDL3/GSDMA and IL2RB) of ten loci recently reported to be associated with asthma were associated with T1D (p≤0.005). CONCLUSIONS: These results show that there are shared genetic associations for atopy-related traits and T1D, and this might help in the future to understand the mechanisms, pathways and environmental factors that underpin the rapid rise in incidence of both disorders in children.