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1.
Cell ; 186(6): 1127-1143.e18, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36931243

RESUMO

CD8+ T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment, recent studies in mice identified responses in lymph nodes (LNs) as essential; however, the role of LNs in human cancer patients remains unknown. We examined CD8+ T cells in human head and neck squamous cell carcinomas, regional LNs, and blood using mass cytometry, single-cell genomics, and multiplexed ion beam imaging. We identified progenitor exhausted CD8+ T cells (Tpex) that were abundant in uninvolved LN and clonally related to terminally exhausted cells in the tumor. After anti-PD-L1 immunotherapy, Tpex in uninvolved LNs reduced in frequency but localized near dendritic cells and proliferating intermediate-exhausted CD8+ T cells (Tex-int), consistent with activation and differentiation. LN responses coincided with increased circulating Tex-int. In metastatic LNs, these response hallmarks were impaired, with immunosuppressive cellular niches. Our results identify important roles for LNs in anti-tumor immune responses in humans.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Humanos , Animais , Camundongos , Linfonodos , Neoplasias/terapia , Neoplasias/patologia , Imunoterapia/métodos , Microambiente Tumoral
2.
Int J Psychiatry Med ; 58(3): 284-294, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35430921

RESUMO

OBJECTIVES: Somatic symptom disorder (SSD) is a diagnostic classification to describe the occurrence of physical symptoms without organic cause. This study aimed to identify prevalence rates and associated characteristics of SSD among adults in primary care settings. METHODS: This cross-sectional study took place between July 2020 and March 2021 and included a random selection of 3383 Omani adults attending 12 primary healthcare centres in Muscat Governorate. Screening was conducted using an Arabic version of the Somatic Symptom Scale-8 (SSS-8). RESULTS: A total of 2000 adults participated in the study (response rate: 67.3%), of which most were female (71.7%) and under 50 years old (86.2%). Based on their SSS-8 scores, 602 participants (17.8%) had SSD, resulting in an overall prevalence estimate of 30.1% (95% confidence interval: 28.13-32.15). Significant associations were observed between SSD and age (p = 0.002), gender (p < 0.001), marital status (p = 0.030) and chronic comorbidities (p = 0.001). In addition, adjusted odds ratio estimates revealed SSD to be significantly associated with gender (p < 0.001), education level (p < 0.001) and chronic comorbidities (p = 0.001). CONCLUSION: The estimated prevalence of SSD in primary care settings is high compared to reports from elsewhere in the Gulf region. There is an urgent need to enhance the diagnosis of SSD at the primary care level in order to reduce healthcare service overutilisation and patient dissatisfaction. Moreover, healthcare practitioners should be aware of the effect of age, gender, educational status and chronic comorbidities on somatic symptoms.


Assuntos
Sintomas Inexplicáveis , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Omã/epidemiologia , Inquéritos e Questionários , Transtornos Somatoformes/diagnóstico , Transtornos Somatoformes/epidemiologia , Prevalência , Atenção Primária à Saúde
3.
Pharm Dev Technol ; 28(9): 884-895, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37830868

RESUMO

PURPOSE: Asses the wound healing activity of Polyvinyl alcohol - Deflazacort (PVA-DEF) nanofibers mats synthesized by electrospinning technology. METHODS: PVA-DEF nanofiber mats were created with various PVA polymer concentrations using an electrospinning process. The morphological features and diameter of the electrospun nanofibrous mats were investigated using scanning electron microscopy (SEM). The in vitro DEF release rate from PVA electrospun nanofibrous mats was evaluated. In addition to assessing wound healing activity in vivo, histological, and immunochemical tests were conducted. RESULTS: Results revealed a uniform and smooth surface of the fiber with an average diameter of the selected fibers of 533.9 nm ± 45.83. Also, PVA electrospun nanofiber mats showed an initial burst release of more than 50% of the DEF in 1 h, and the rest of the DEF was released gradually for up to 480 min. Fickian diffusion is the main DEF release mechanism from PVA electrospun nanofiber mats. In male Wistar albino rats with 1 cm2 excision wounds, in vivo studies revealed a significant improvement in wound healing rate via modulation of tumor necrosis factor-alpha (TNF-α) and vascular endothelial growth factor (VEGF) expression. CONCLUSION: PVA-DEF nanofiber mats can be used effectively for improving wound healing.


Assuntos
Quitosana , Nanofibras , Ratos , Animais , Masculino , Fator A de Crescimento do Endotélio Vascular , Cicatrização , Álcool de Polivinil , Ratos Wistar , Anti-Inflamatórios/farmacologia
4.
Anal Chem ; 94(41): 14185-14194, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36190014

RESUMO

The excited-state lifetime is an intrinsic property of fluorescent molecules that can be leveraged for multiplexed imaging. An advantage of fluorescence lifetime-based multiplexing is that signals from multiple probes can be gathered simultaneously, whereas traditional spectral fluorescence imaging typically requires multiple images at different excitation and emission wavelengths. Additionally, lifetime and spectra could both be utilized to expand the multiplexing capacity of fluorescence. However, resolving exogenous molecular probes based exclusively on the fluorescence lifetime has been limited by technical challenges in analyzing lifetime data. The phasor approach to lifetime analysis offers a simple, graphical solution that has increasingly been used to assess endogenous cellular autofluorescence to quantify metabolic factors. In this study, we employed the phasor analysis of FLIM to quantitatively resolve three exogenous, antibody-targeted fluorescent probes with similar spectral properties based on lifetime information alone. First, we demonstrated that three biomarkers that were spatially restricted to the cell membrane, cytosol, or nucleus could be accurately distinguished using FLIM and phasor analysis. Next, we successfully resolved and quantified three probes that were all targeted to cell surface biomarkers. Finally, we demonstrated that lifetime-based quantitation accuracy can be improved through intensity matching of various probe-biomarker combinations, which will expand the utility of this technique. Importantly, we reconstructed images for each individual probe, as well as an overlay of all three probes, from a single FLIM image. Our results demonstrate that FLIM and phasor analysis can be leveraged as a powerful tool for simultaneous detection of multiple biomarkers with high sensitivity and accuracy.


Assuntos
Corantes Fluorescentes , Imagem Óptica , Microscopia de Fluorescência/métodos , Imagem Molecular , Sondas Moleculares
5.
Drug Dev Ind Pharm ; 48(12): 683-693, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36533708

RESUMO

OBJECTIVE: The purpose of this work was to improve EP solubility by using a sono-crystalization approach to reduce particle size and hence, increase the dissolution rate. Significance Eplerenone (EP) is an antagonist of the aldosterone receptor and is used for the treatment of hypertension and chronic heart failure. EP was classed as biopharmaceutical classification (BCS) class II because of its poor solubility and high permeability, which retards dissolution rate and drug absorption, and decreases bioavailability. METHODS: Three-factors and two-level (23) multifactorial design have been employed to study the effect of independent variables which are drug concentration; (X1), stabilizer type (X2), and stabilizer concentration (X3) on responses; saturated solubility of EP in distilled water (Y1), saturated solubility in acidic media pH 1.2 (Y2), particle size (Y3), and polydispersity index, PDI (Y4). Also, they were characterized by Fourier transformed infrared spectroscopy (FTIR), Powder X-ray diffraction (PXRD), Differential scanning calorimetry (DSC), and yield percentage. The optimum formula was further subjected to an in-vitro release study. RESULTS: The optimized formulation showed a saturated solubility of EP as 1.29, and 1.86 (mg/ml) in distilled water and acidic media (pH 1.2) respectively. Also, the particle size of 133 nm, and PDI of 0.824 with a small percentage of the difference between the observed and predicted values. Ninety-one percent of EP was released within 10 min., and it was completely released within 45 min. with a significantly higher release rate compared to raw drug. CONCLUSION: This work resulted in a satisfactory enhancement of solubility and dissolution rate which, is suitable for further in-vivo analysis.


Assuntos
Nanopartículas , Água , Solubilidade , Solventes/química , Eplerenona , Cristalização , Água/química , Tamanho da Partícula , Varredura Diferencial de Calorimetria , Disponibilidade Biológica , Difração de Raios X , Nanopartículas/química
6.
Health Qual Life Outcomes ; 19(1): 39, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33531025

RESUMO

BACKGROUND: Chronic kidney disease is considered as a global health problem. Hemodialysis (HD), following renal transplantation, is the most common form of renal replacement therapy. However, HD may impact the quality of life (QOL). Pain is a frequent complaint among this population that also affects their QOL. The purposes of this study were to assess pain and QOL among end-stage renal disease (ESRD) patients on HD and to examine their association. METHODS: This was a multicenter, cross-sectional study that occurred in Palestine between August and November 2018. Brief Pain Inventory and European Quality of Life scale 5 dimensions (EQ-5D) scale, including its European Quality of Life visual analogue scale (EQ-VAS) component, were used to assess pain and QOL, respectively. RESULTS: A total of 300 participants were included in the final study. The average age of the subjects was 54 ± 16 years. Their median EQ-5D score was 0.68 [0.54-0.88], whereas their median EQ-VAS score was 60 [40-75]. A statistically significant association of pain severity score with EQ-5D score was found (r = - 0.783, p < 0.001). The association between pain interference score and EQ-5D score was also found to be statistically significant (r = - 0.868, p < 0.001). Similarly, pain severity score was significantly assocsiated with EQ-VAS score (r = - 0.590, p < 0.001), the same as was the pain interference score (r = - 0.647, p < 0.001). Moreover, age, gender, BMI, employment, educational level, income level, dialysis vintage, previous kidney transplantation, and chronic medication use were all significantly correlated with QOL. Regression analysis showed that patients aged < 60 years (p < 0.001), those with lower pain severity scores (p = 0.003), and those with lower pain interference scores (p < 0.001) had significantly higher QOL scores. CONCLUSIONS: Pain has a significant negative impact on QOL in ESRD patients undergoing HD. The subgroups that were at higher risk included elderly patients, females, those with higher BMI, those without a formal education, those unemployed, those living with low monthly income, smokers, those who have multiple comorbidities, and patients with longer dialysis vintage. Our findings provide reliable data for educators and clinicians working with HD patients.


Assuntos
Falência Renal Crônica/psicologia , Falência Renal Crônica/terapia , Qualidade de Vida/psicologia , Diálise Renal/psicologia , Adulto , Idoso , Comorbidade , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Diálise Renal/efeitos adversos
7.
BMC Nephrol ; 22(1): 96, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731036

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is a rising medical concern around the world. End-stage kidney disease (ESKD) is the last stage of CKD stages that necessitates renal replacement therapy (RRT), such as hemodialysis (HD), which seems to be the most commonly used type. However, patients on HD still suffer from high mortality and morbidity rates compared to those who receive a kidney transplant. Therefore, we aimed in this study to assess the prevalence of pain among ESKD patients on HD, as well as to explore the factors that were associated with this complaint. METHODS: We conducted a multicenter cross-sectional study in the West Bank, Palestine, between August and November 2018. We used questionnaire-based direct interviews with subjects. After reviewing previous studies in the field, we developed our questionnaire and included items on patients' social, demographic, and clinical characteristics, including dialysis-related data. It also contained the Brief Pain Inventory (BPI) to assess different aspects of pain symptoms. A convenience sampling technique was used to collect data. RESULTS: Of the 300 participants, 66.3 % reported having chronic pain. HD sessions themselves were the most commonly cited cause for pain (21.6 %). The most commonly cited site of pain was the upper and lower limbs (37.3 %). Paracetamol was the most frequently used pharmacotherapy for pain alleviation. Multiple regression analysis showed that BMI (p = 0.018), gender (p = 0.023), and the number of comorbidities (p < 0.001) were independently associated with pain severity score. CONCLUSIONS: Pain is a highly prevalent symptom among HD patients in Palestine. Subpopulations with higher pain severity include females, patients with higher BMI, and those with multiple comorbidities. Healthcare providers should routinely assess pain in HD patients as it is considered a significant concern. This would involve pain assessment and development of a treatment plan to improve clinical outcomes. The nephrology associations should also push for pain management in HD patients as a clinical and research priority to improve pain-related disability.


Assuntos
Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Dor/epidemiologia , Dor/etiologia , Diálise Renal , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oriente Médio , Prevalência
8.
Int J Toxicol ; 40(4): 388-394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34044595

RESUMO

BACKGROUND: The sudden emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and scarcity of the accurate information especially in the initial phase of the struggle presented a series of challenges to health systems. OBJECTIVE: To evaluate the changes in poisoning cases regarding distribution, types, and characteristics for better framing and planning of the role of our field in responding to pandemics. METHODS: Study of telephone consultation calls and toxicology analysis records of poisoning cases referred to the Dammam Poison Control Center in Saudi Arabia during the first half of 2020. Their distribution according to frequencies, causes, and other characteristics was compared to the first half of 2019. RESULTS: Analysis of telephone consultation calls revealed that the proportion of exposure to disinfectants and hand sanitizers during first half of 2020 increased to 20.4% (n = 496) and 3.4% (n = 83), respectively, compared to 9.8% (n = 215) and 0.4% (n = 10) for surface disinfectants and hand sanitizers, respectively, during the first half of 2019. In 2020, exposure to disinfectants and hand sanitizers dominated in preschool children (0-5 years). The total number of cases suspected for drugs/drugs of abuse overdose during the first 6 months of 2020 (n = 783) showed a significant decrease (P < 0.001) compared to the first 6 months of 2019 (n = 1086). CONCLUSION: The increased availability and use of disinfectants and sanitizers significantly increased the risk of poisoning, especially in preschool-aged children. Public health education for prevention of such home exposures is urgently needed to avoid unnecessary emergency medical system use in such critical time.


Assuntos
COVID-19/epidemiologia , Desinfetantes/toxicidade , Higienizadores de Mão/toxicidade , Centros de Controle de Intoxicações/estatística & dados numéricos , Encaminhamento e Consulta , SARS-CoV-2 , Pré-Escolar , Humanos , Arábia Saudita/epidemiologia , Fatores de Tempo
9.
BMC Infect Dis ; 20(1): 436, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32571225

RESUMO

BACKGROUND: Thyroid gland infections are rare. Their incidence is estimated to be less than 1% in immunocompromised hosts. Most common pathogens isolated are Gram positive aerobic cocci. Infections with Gram negative facultative aerobes such as Salmonella are rare. CASE PRESENTATION: A 55-year-old female with type II diabetes mellitus and a history of a colloid right thyroid lobe nodule presented with neck pain and fever. She was found to have a thyroid abscess 2 weeks following a non-specific diarrheal illness. A needle aspiration for symptomatic and diagnostic purposes was performed. Cultures grew Salmonella enterica serotype Heidelberg. She was treated with a 12-week course of oral antibiotics and serial aspiration. CONCLUSION: A thyroid abscess is a rare occurrence; however, a high index of suspicion is required to make the diagnosis. The management is directed at minimizing morbidity. The mainstay treatment is medical, but surgery is sometimes necessary to achieve adequate source control, particularly when complications arise.


Assuntos
Abscesso/microbiologia , Infecções por Salmonella/complicações , Infecções por Salmonella/tratamento farmacológico , Tireoidite Supurativa/tratamento farmacológico , Tireoidite Supurativa/microbiologia , Abscesso/diagnóstico , Abscesso/terapia , Antibacterianos/uso terapêutico , Ciprofloxacina/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Dor/etiologia , Salmonella/patogenicidade , Infecções por Salmonella/diagnóstico , Tireoidite Supurativa/etiologia
10.
J Cosmet Sci ; 71(5): 321-350, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33022200

RESUMO

Aging is a natural phenomenon that affects the whole body, including the skin. As we age, endogenous and exogenous factors cause our skin to become thinner, paler, and wrinkled. Although the underlying mechanisms of the pathogenesis of skin aging are not entirely known, multiple pathways have been proposed. Inflammaging has recently emerged as a pathway that correlates aging and age-related diseases with inflammation. This review discusses the role and pathways of inflammaging that lead to skin aging. Moreover, strategies and current topical approaches for skin-aging treatment are discussed. Studies over the past 10 years suggested that DNA damage and oxidative stress are the most critical mechanisms in skin aging, and both are interlinked with inflammaging. Several treatments for skin aging have been considered such as antioxidants, hormone replacement therapy, and vitamins. To deliver anti-aging agents topically, researchers adopted numerous approaches to enhance skin penetration including physical, chemical, or biomaterial enhancers and carrier-based formulations. In recent years, consumers' demands for anti-aging products have considerably risen, leading to robust growth in the anti-aging market. Therefore, further in-depth studies are necessary to understand skin-aging mechanisms and evaluate the efficacy of anti-aging products to protect consumers worldwide by providing them safe and effective over-the-counter skin-aging formulations.


Assuntos
Envelhecimento da Pele , Antioxidantes/farmacologia , Humanos , Inflamação , Pele
11.
Analyst ; 144(3): 980-989, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30270391

RESUMO

Single cell analysis methods are increasingly being utilized to investigate how individual cells process information and respond to diverse stimuli. Soluble proteins play a critical role in controlling cell populations and tissues, but directly monitoring secretion is technically challenging. Microfabricated well arrays have been developed to assess secretion at the single cell level, but these systems are limited by low detection sensitivity. Semiconductor quantum dots (QD) exhibit remarkably bright and photostable luminescence signal, but to date they have not been evaluated in single cell secretion studies using microfabricated well arrays. Here, we used QDs in a sandwich immunoassay to detect secretion of the soluble cytokine tumor necrosis factor-α (TNF-α) from single cells. To enhance detection sensitivity, we employed two different strategies. First, we used a unique single QD imaging approach, which provided a detection threshold (180 attomolar) that was >100-fold lower than previously reported results using QDs. We also amplified QD binding to each captured TNF-α molecule using the bioorthogonal cycloaddition reaction between trans-cyclooctene and tetrazine, which further lowered detection threshold to 60 attomolar. This is 6 orders of magnitude more sensitive than organic fluorophores that have been used for single cell secretion studies, and far surpasses single molecule resolution within sub-picoliter microwells that are used to assess single cell secretion. Finally, single cell secretion studies were performed using phorbol 12-myristate 13-acetate (PMA) differentiated and lipopolysaccharide (LPS) activated U-937 cells. TNF-α secretion was detected from 3-fold more single cells using the QD-based method in comparison to rhodamine, which was accomplished by extending sensitivity into the range of ∼2 to 10 000 molecules captured per microwell. In future work, we will apply this technique to assess immune cell secretion dynamics under diverse stimuli and disease settings. We will also incorporate multiplexing capabilities to evaluate the secretome at the resolution of single molecules.


Assuntos
Imunoensaio/métodos , Pontos Quânticos , Análise de Célula Única/métodos , Fator de Necrose Tumoral alfa/análise , Humanos , Limite de Detecção , Células U937
12.
Cell Mol Biol (Noisy-le-grand) ; 64(1): 84-90, 2018 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-29412799

RESUMO

Obesity is a multifactor disorder with evidence supporting the role of the genetic factor in its etiology. The present study evaluates the relationship between leptin G2548A (rs7799039) and leptin receptors (Gln223Arg (rs1137101) genotyping and its leptin level and the risk of childhood obesity. This case-control study was conducted on 168 overweight and obese Saudi children and 126 non obese one served as control. Fasting insulin, leptin, blood glucose, lipid profile levels were measured. HOMA- IR, and BMI were assessed. Genotyping of leptin and leptin receptor gene variants was done by SNP real-time PCR method. GG genotype and G allele of rs1137101 were significantly higher in overweight and obese children than controls. It showed significant association with risk of obesity OR 7.1 [ 95% CI: 3.4 - 14.8] and OR 2.8 [ 95% CI: 2.0 - 4.1] respectively. Leptin level was significantly greater in patients than controls (p<0.000*) with GG and AG genotypes having the highest level of leptin when compared with another genotype in the obese group. As regards, rs7799039 AA genotype showed significant higher leptin level than other genotypes in the same group with a non-significant difference in genotypes distribution between obese and controls. rs1137101 variant of leptin receptor and fasting leptin level are correlated with overweight and obesity in Saudi children. The GG genotype of leptin receptors rs1137101 and higher serum leptin levels can be used as risk factors for childhood obesity.


Assuntos
Leptina/sangue , Leptina/genética , Obesidade/genética , Sobrepeso/genética , Tamanho Corporal , Estudos de Casos e Controles , Criança , Feminino , Expressão Gênica , Humanos , Masculino , Obesidade/sangue , Sobrepeso/sangue , Polimorfismo de Nucleotídeo Único , Receptores para Leptina/genética
13.
Cell Mol Biol (Noisy-le-grand) ; 64(5): 7-12, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29729689

RESUMO

Uterine smooth muscle tumors constitute a spectrum of neoplasms. Diagnosis of leiomyomas (LMs) is usually straight forwards; however, atypical leiomyomas (ALMs) and smooth muscle tumors of uncertain malignant potential (STUMPs) have overlapping features and need to be distinguished from leiomyosarcoma. To evaluate progesterone receptor (PR), epithelial growth factor receptor (EGF-R), and galectin-3 expression in LMs, ALMs, STUMPs, and leiomyosarcomas and to assess their possible role in differentiating those tumors. Immunoexpression of EGF-R, PR, and galectin-3 were studied in 44 cases of uterine smooth muscle tumors through retrospective study. Studied cases included 20 LM, 9 ALM, 5 STUMP, and 10 leiomyosarcomas. A semiquantitative score was used to evaluate immunohistochemical staining. EGF-R overexpression was detected in leiomyosarcomas while a lack of or reduced EGF-R expression was observed in the nonsarcomatous group (LMs, ALMs, and STUMPs) with a highly significant difference. On the contrary, there was weak or negative PR staining in leiomyosarcomas compared to intense PR expression in the nonsarcomatous group with a highly significant difference. Meanwhile, galectin-3 was downregulated in leiomyosarcomas compared to the nonsarcomatous group with a significant difference. Correlation analysis revealed negative correlation between EGF-R and PR expression with significant statistical results while correlation of galectin-3 with EGF-R and PR showed insignificant statistical results. Immunoexpression of EGF-R, PR, and galectin-3 could help differentiate challenging cases of uterine smooth muscle tumors. Further studies are recommended to investigate interactions between EGF-R, PR, and galectin-3 and to plan new therapeutic strategies.


Assuntos
Biomarcadores Tumorais/genética , Receptores ErbB/genética , Galectina 3/genética , Leiomioma/diagnóstico , Leiomiossarcoma/diagnóstico , Receptores de Progesterona/genética , Tumor de Músculo Liso/diagnóstico , Biomarcadores Tumorais/metabolismo , Proteínas Sanguíneas , Estudos de Casos e Controles , Diagnóstico Diferencial , Receptores ErbB/metabolismo , Feminino , Galectina 3/metabolismo , Galectinas , Humanos , Imuno-Histoquímica , Leiomioma/genética , Leiomioma/metabolismo , Leiomioma/patologia , Leiomiossarcoma/genética , Leiomiossarcoma/metabolismo , Leiomiossarcoma/patologia , Receptores de Progesterona/metabolismo , Estudos Retrospectivos , Tumor de Músculo Liso/genética , Tumor de Músculo Liso/metabolismo , Tumor de Músculo Liso/patologia , Incerteza , Útero/metabolismo , Útero/patologia
14.
Langmuir ; 32(49): 13124-13136, 2016 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-27797529

RESUMO

The targeted delivery of nanoparticle carriers holds tremendous potential to transform the detection and treatment of diseases. A major attribute of nanoparticles is the ability to form multiple bonds with target cells, which greatly improves the adhesion strength. However, the multivalent binding of nanoparticles is still poorly understood, particularly from a dynamic perspective. In previous experimental work, we studied the kinetics of nanoparticle adhesion and found that the rate of detachment decreased over time. Here, we have applied the adhesive dynamics simulation framework to investigate binding dynamics between an antibody-conjugated, 200-nm-diameter sphere and an ICAM-1-coated surface on the scale of individual bonds. We found that nano adhesive dynamics (NAD) simulations could replicate the time-varying nanoparticle detachment behavior that we observed in experiments. As expected, this behavior correlated with a steady increase in mean bond number with time, but this was attributed to bond accumulation only during the first second that nanoparticles were bound. Longer-term increases in bond number instead were manifested from nanoparticle detachment serving as a selection mechanism to eliminate nanoparticles that had randomly been confined to lower bond valencies. Thus, time-dependent nanoparticle detachment reflects an evolution of the remaining nanoparticle population toward higher overall bond valency. We also found that NAD simulations precisely matched experiments whenever mechanical force loads on bonds were high enough to directly induce rupture. These mechanical forces were in excess of 300 pN and primarily arose from the Brownian motion of the nanoparticle, but we also identified a valency-dependent contribution from bonds pulling on each other. In summary, we have achieved excellent kinetic consistency between NAD simulations and experiments, which has revealed new insights into the dynamics and biophysics of multivalent nanoparticle adhesion. In future work, we will leverage the simulation as a design tool for optimizing targeted nanoparticle agents.


Assuntos
Anticorpos/química , Molécula 1 de Adesão Intercelular/química , Nanopartículas/química , Biofísica , Cinética
15.
Bioconjug Chem ; 26(2): 352-60, 2015 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-25584926

RESUMO

The bioorthogonal cycloaddition reaction between tetrazine and trans-cyclooctene (TCO) is rapidly growing in use for molecular imaging and cell-based diagnostics. We have surprisingly uncovered that the majority of TCOs conjugated to monoclonal antibodies using standard amine-coupling procedures are nonreactive. We show that antibody-bound TCOs are not inactivated by trans-cis isomerization and that the bulky cycloaddition reaction is not sterically hindered. Instead, TCOs are likely masked by hydrophobic interactions with the antibody. We show that introducing TCO via hydrophilic poly(ethylene glycol) (PEG) linkers can fully preserve reactivity, resulting in >5-fold enhancement in functional density without affecting antibody binding. This is accomplished using a novel dual bioorthogonal approach in which heterobifunctional dibenzylcyclooctyne (DBCO)-PEG-TCO molecules are reacted with azido-antibodies. Improved imaging capabilities are demonstrated for different cancer biomarkers using tetrazine-modified fluorophore and quantum dot probes. We believe that the PEG linkers prevent TCOs from burying within the antibody during conjugation, which could be relevant to other bioorthogonal tags and biomolecules. We expect the improved TCO reactivity obtained using the reported methods will significantly advance bioorthogonal pretargeting applications.


Assuntos
Ciclo-Octanos/química , Imunoconjugados/química , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Azidas/química , Azidas/imunologia , Linhagem Celular Tumoral , Reação de Cicloadição , Receptores ErbB/análise , Humanos , Imunoconjugados/imunologia , Isomerismo , Camundongos , Modelos Moleculares , Imagem Óptica , Polietilenoglicóis/química
16.
Sci Rep ; 14(1): 5670, 2024 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453979

RESUMO

The GPT-4 large language model (LLM) and ChatGPT chatbot have emerged as accessible and capable tools for generating English-language text in a variety of formats. GPT-4 has previously performed well when applied to questions from multiple standardized examinations. However, further evaluation of trustworthiness and accuracy of GPT-4 responses across various knowledge domains is essential before its use as a reference resource. Here, we assess GPT-4 performance on nine graduate-level examinations in the biomedical sciences (seven blinded), finding that GPT-4 scores exceed the student average in seven of nine cases and exceed all student scores for four exams. GPT-4 performed very well on fill-in-the-blank, short-answer, and essay questions, and correctly answered several questions on figures sourced from published manuscripts. Conversely, GPT-4 performed poorly on questions with figures containing simulated data and those requiring a hand-drawn answer. Two GPT-4 answer-sets were flagged as plagiarism based on answer similarity and some model responses included detailed hallucinations. In addition to assessing GPT-4 performance, we discuss patterns and limitations in GPT-4 capabilities with the goal of informing design of future academic examinations in the chatbot era.


Assuntos
Educação de Pós-Graduação , Alucinações , Humanos , Conhecimento , Idioma , Estudantes
17.
Cureus ; 16(7): e64577, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39011315

RESUMO

Anterior spinal artery syndrome (ASAS) is a rare form of spinal cord infarction, making its incidence and prevalence difficult to determine. We present the case of a 60-year-old woman with multiple vascular risk factors who experienced a sudden onset of severe lower limb weakness, raising immediate concerns about spinal cord ischemia. Diagnostic evaluations confirmed ASAS, although the exact cause and mechanism of her spinal cord infarction remained undetermined. The potential presence of significant cervical disc disease suggests fibrocartilaginous embolism (FCE) as a possible underlying mechanism, despite the lack of direct evidence. This case underscores the importance of clinical awareness and timely intervention in patients with similar symptoms and vascular risk factors. Early recognition, cause identification, and appropriate management are crucial for improving outcomes in spinal cord ischemia, guiding specific treatment strategies, and potentially preventing recurrence.

18.
Cureus ; 16(8): e66052, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39224746

RESUMO

Background Narcolepsy is a chronic sleep disorder that is characterized by excessive daytime sleepiness and cataplexy. It has been increasingly diagnosed over the years, impacting productivity and employment rates. Awareness of healthcare providers is crucial for the early identification and management of this condition. Objectives This study assessed physicians' knowledge of narcolepsy in the Makkah region of Saudi Arabia. Method This cross-sectional study was conducted from February to November 2023. An online self-administered questionnaire has been used to target physicians working in the Makkah region of Saudi Arabia. The utilized questionnaire assessed demographic and professional data as well as the participants' knowledge of narcolepsy. Statistical analysis was performed using RStudio (R version 4.3.1.). Statistical differences in knowledge were assessed using Pearson's chi-squared and Fisher's exact tests. Factors associated with knowledge of narcolepsy were investigated through univariable and multivariable regression analyses expressed using beta coefficients and 95% confidence intervals (95% CIs). Statistical significance was considered at p < 0.05. Results A total of 226 physicians participated in this study. Male physicians (54.4%, n = 123), practicing in governmental hospitals (77.9%, n = 176) and residing in Makkah City (43.4%, n = 98) were predominant. Non-surgical specialties represented 73.5% (n = 166) of the sample. Around 81% (n = 184) of the participants were aware of narcolepsy, with a significant difference according to professional status (p = 0.045). The majority of physicians have correctly identified narcolepsy as a sleep disorder (78.3%, n = 177), but only 32.3% (n = 73) have identified its typical onset age group and recognized that there are two types of narcolepsy. Almost half of the respondents indicated a lack of knowledge about the diagnostic criteria for narcolepsy in the DSM-5 (52.2%, n = 118). Only 27.4% (n = 62) recognized the correct diagnostic criteria. Half of the sample (51.3%, n = 116) recognized the use of multiple sleep latency tests for the diagnosis. For factors associated with higher participants' knowledge, non-surgical specialties showed significantly higher knowledge scores compared to surgical specialties (beta = 0.91, 95% CI, 0.13 to 1.7, p = 0.024). Conclusion This study has revealed a significant lack of knowledge about narcolepsy among physicians in Makkah region. This raises concerns about the timely identification, proper understanding, and accurate diagnosis of patients with narcolepsy. Adequate understanding of narcolepsy is crucial to avoid its misdiagnosis or delays in receiving appropriate treatment and support, ultimately impacting their quality of life.

19.
Cureus ; 16(3): e56759, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38650788

RESUMO

Background and aim A healthy lifestyle is defined as a way of living that reduces the likelihood of severe illness or early death. Factors required for a healthy lifestyle, such as regular physical activity, better sleep patterns, improved dietary habits, probable caffeine consumption, and decreased feelings of anxiety, are generally assumed to be important for high academic performance. This study aims to investigate the correlation between a healthy lifestyle and academic success among health profession students at Umm Al-Qura University, Saudi Arabia. By doing so, we could potentially lead to the implementation of targeted interventions to support students in achieving their best academic potential. Methods This is an observational cross-sectional study conducted among health profession students at Umm Al-Qura University. An online questionnaire was used to collect data on demographic information and the impact of lifestyle characteristics on academic performance from October to November 2023. Data were analyzed using RStudio (R version 4.3.1). Results A total of 652 students participated in the study. The majority were between the ages of 18 and 25 years (97.2%, n=634). Females constituted the majority of the participants (69.9%, n=456). Regarding the field of study, the College of Medicine had the highest representation (52.9%, n=345). Regarding body mass index, the normal weight category was the most prevalent, encompassing 59.8% (n=390) of the participants. The results show that the participants generally had a good grade point average (GPA) in the range of 3.50 to 4.00. Also, the time spent on social media applications was not correlated with academic performance (P=0.575). Importantly, the majority of participants perceived that lifestyle habits impacted their academic performance. Conclusion This study found that unhealthy lifestyle factors, such as lack of physical activity, inadequate sleep, poor dietary choices, smoking, and mental health issues such as anxiety, have a negative impact on academic performance. Therefore, the dissemination of relevant knowledge is needed to promote the importance of a healthy lifestyle and raise students' awareness.

20.
Cureus ; 16(6): e61990, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38989347

RESUMO

BACKGROUND:  Pediatric ear infections constitute a significant public health concern worldwide, adversely impacting children's health and well-being. Parents play a crucial role in prevention, ensuring timely healthcare access, and therefore minimizing potential complications. This study aims to assess parental knowledge, attitudes, and practices towards pediatric ear infections in Makkah region. METHODOLOGY:  A descriptive cross-sectional study was conducted among Saudi parents who were ≥18 years old and lived in Makkah region. Convenience sampling was used to recruit 319 participants through social media platforms; data were collected from June to September 2023 via an online self-administered questionnaire. The questionnaire assessed sociodemographic characteristics, along with knowledge, attitudes, and practices related to pediatric ear infections. RESULTS:  A total of 319 parents were included in the study. The majority of the participants were female 228 (71.5%), and 208 (65.2%) had a university education level. The most common age groups were 18-30 years and 31-40 years. More than half of the participants (167, 52.4%) demonstrated adequate knowledge regarding pediatric ear infections. Positive attitudes and practices were reported by 183 (57.4%) and 285 (89.3%) of participants, respectively. Adequate knowledge was significantly higher among participants with younger ages (p<0.05). It was found that having a younger age (18-30 years) was an independent predictor of good knowledge (OR: 1.26 (1.96-3.65), p=0.009) and positive practice (OR: 1.53 (1.01-2.33), p=0.045). CONCLUSION:  We found that the majority of parents in Makkah region had a good level of knowledge regarding childhood ear infections, with an overall positive attitude and practice. The study revealed that younger parents had superior knowledge and younger age was an independent predictor for good knowledge and positive attitude.

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