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Background: Gold nanoparticles (GNPs) are among the most promising radiosensitive materials in radiotherapy. Studying the effective sensitizing factors such as nanoparticle size, concentration, surface features, radiation energy and cell type can help to optimize the effect and possible clinical application of GNPs in radiation therapy. In this study, the radiation sensitive polymer gel was used to investigate the dosimetric effect of GNP size in megavoltage (MV) photon beam radiotherapy. Material and Methods: GNPs with the size of 30nm, 50nm and 100nm in diameter were used. Transmission electron microscope (TEM) and dynamic light scattering (DLS) were applied to analyze the size of nanoparticles. The MAGICA polymer gel was synthesized and impregnated with different sizes of GNPs. The samples were irradiated with 6MV photon beam and 24 hours after irradiation, they were read using a Magnetic Resonance Imaging (MRI) scanner. Macroscopic Dose Enhancement Factor (DEF) was measured to compare the effect of GNP size. The MAGICA response of the 6MV x-ray beam was verified comparing Percentage Depth Dose (PDD) curve extracted from polymer gel dosimetry and Treatment Planning System (TPS). Results: MAGICA polymer gel dose response curve was linear in the range of 0 to 10 Gy. DEFs by adding 30nm, 50nm and 100nm GNPs were 1.1, 1.17 and 1.12, respectively. PDD curves of polymer gel dosimeter and treatment planning system were in good agreement. Conclusion: The results indicated a substantial increase in DEF uses a MV photon beam in combination with GNPs of different sizes and it was inconsistent with previous radiobiological studies. The maximum DEF was achieved for 50nm GNPs in comparison with 30nm and 100nm leading to the assumption of self-absorption effect by larger diameters. According to the outcomes of this work, MAGICA polymer gel can be recommended as a reliable dosimeter to investigate the dosimetric effect of GNP size and also a useful method to validate the current radiobiological and simulation studies.

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Background: The use of medicinal plants due to their lower side effects and the various efficient components has been increased in recent years. The aim of this study was to evaluate the antinociceptive effect of hydroalcoholic extract of green tea in male mice using the hot plate and formalin tests. Materials and Methods: In this experimental study, 56 NMRI male mice (weight, 28±3 g) were assigned to the control and experimental groups. The experimental group received the green tea extract (75, 150 and 300 mg/kg) and 30 min after the injection, the hot plate and formalin tests were used to assess the acute and chronic pain. Results: Results showed that hydroalcoholic extract of green tea (75mg/kg) could induce antinociception in phase 2, not in phase 1 and interphase of the formalin test. Hydroalcoholic extract of green tea (150 and 300 mg/kg) could also induce antinociception in phase 1, interphase and phase 2 of the formalin test. Moreover, hydroalcoholic extract of green tea caused a delay on the painful behaviors in hot-plate test. Conclusion: Hydroalcoholic extract of green tea has analgesic properties and can be used as a substitute for chemical analgesic drugs. [ABSTRACT FROM AUTHOR]

Background: Diabetes is the sixth main cause of mortality in the world, and its both types are accompanied with eye complications in a way that the risk of blindness in diabetic patients is 25 times more than normal people. Hence, this study was conducted to determine diabetic patients' awareness of the eye complications associated with this disease. Materials and Methods: In a cross-sectional study, 200 diabetic patients referring to the eye clinic of Amir Kabir Hospital of Arak in 2008 were evaluated. Data collection was done through questionnaire and referral interviews. Then some of the factors affecting patients' awareness of eye complications associated with diabetes were analyzed. Results: The level of awareness of eye complications associated with diabetes in 40% of the patients was average. Also, significant relationships were observed between the level of awareness and age, job, education, type of retinopathy, type of treatment, and the history of referring to ophthalmologist (p<0.001), whereas no significant relationships were observed between the level of awareness and gender, familial history of diabetes, and controlling the diet (p>0.05). Conclusion: This study showed that a higher level of awareness in diabetic patients does not necessitate that they observe a proper diet, but it can lead to patients' greater care in preventing the development of diabetes. [ABSTRACT FROM AUTHOR]

Context.--The immunohistochemical identification of thyroid transcription factor-1 (TTF-1) is regarded as the presence of a nuclear pattern of staining and is used to identify tumors of thyroid or pulmonary origin. Although there have been reports of cytoplasmic expression of TTF-1, the significance of this pattern has not been studied in detail. Objectives.--To determine the incidence at which cytoplasmic immunostaining for TTF-1 occurs and to analyze the diagnostic value of this pattern of immunoreactivity. Design.--Histologic sections of 361 consecutive cases of neoplasms stained for TTF-1 were reviewed, and those showing cytoplasmic staining in the tumor cells or in non-neoplastic cells were selected. Clinical correlation was obtained on the latter cases regarding the origin of the tumor. Setting.--An immunohistochemistry laboratory in a tertiary-care institution. Results.--The 361 tumors were obtained from 29 organ sites and corresponded to primary and metastatic neoplasms. Twenty-three (6.3%) tumors showed cytoplasmic staining for TTF-1. In 13 of these, the primary site of origin was established with certainty: 7 were lung carcinomas (3 primary lung adenocarcinomas, 1 primary large cell carcinoma, 1 metastatic small cell carcinoma to the liver, 1 metastatic adenocarcinoma to a neck lymph node, and 1 metastatic adenocarcinoma to thigh soft tissue), 3 colonic adenocarcinomas (2 metastases to vertebrae and 1 to lung), 1 metastatic breast ductal adenocarcinoma to femur, 1 metastatic laryngeal squamous cell carcinoma to liver, and 1 meningioma involving the orbit bone. There were 3 lung carcinomas with concomitant nuclear immunostaining. Nonneoplastic liver tissue was the most frequent non-tumoral tissue in which the cytoplasm stained with TTF-1 antibody. Conclusion.--Occasional cytoplasmic staining for TTF-1 in tumors is seen, but it is a nonspecific finding; when present, it should be disregarded for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Introduction: The finding of a mixture of both 46,XX and 46,XY cells in amniotic fluid culture has been frequently described. In the great majority of cases, the finding is followed by the birth of a normal male infant, leading to a consensus that the finding is the result of contamination with maternal cells in a normal male fetus. There are, however, several other possible explanations including the presence of cells from an undiagnosed twin pregnancy, cross contamination in the laboratory, the presence of cells from a "vanished" male twin, and true fetal chimerism. An accurate obstetric history and thorough sonography can be of great value in correct assessment of such situations. Materials and Methods: A 29 Years-old woman was referred for genetic counseling. Her gestational age was 16 weeks and maternal biochemical serum screening test indicated high risk for Down Syndrome. She underwent amniocentesis for chromosome study using standard high resolution GTG banding technique. Results: Karyotype result was 46,XY and sonography revealed a female fetus with normal internal genital organs. A normal baby girl was borned with 46,XX karyotype. Upon reviewing of amnio GTG slides both 46,XY and 46,XX cell lines were detected. The patient admitted that she had experienced a miscarriage and heavy bleeding early in pregnancy. The sonography at the time of amniocentesis had shown a shrinking cyst next to the fetus. These findings strengthened the vanished or resorbed twin as the reason for such a finding. Conclusion: The fetus was most likely a non-identical twin. Most of grown cells were from the vanished male fetus which led to misdiagnosis. Thorough genetic counseling with the view of obstetric history is of great value in such situations. [ABSTRACT FROM AUTHOR]

Background: Depression is one of the most important psychological problems in society that reduces their health. This study aimed to compare the effectiveness of cognitive-behavioral therapy with behavioral activation therapy on learned helplessness and cognitive emotion regulation in individuals with depressive symptoms. Materials and Methods: The present study was a quasi-experimental pretest and posttest with two experimental groups and a control group. The statistical population of the study included all people with depression in Babol who referred to psychotherapy clinics in 2021. Forty-five subjects who scored above-average on the Beck Depression Inventory were randomly selected and randomly assigned to three groups of 15 responding to the Garnfsky Emotion Cognitive Regulation and Queens and Nelson Learned Helplessness Questionnaire. Analysis of covariance and Benferoni test using SPSS-23 software were used to analyze the results. Results: The results showed that there was no significant difference between the effect of two methods of behavioral methodology and behavioral activation on learned helplessness (P

Starting life in space and implementing spaceflight missions requires raising of plants in special conditions, where various stresses, including microgravity, are applied to plant. The use of stimulants is known as a promising effective approach that enhances plant resistance encountered a variety of abiotic stresses. In this study, the impact of two stimulants, melatonin and chitosan, in reducing negative effects of clinorotation on Rocket (Eruca sativa L.) seedlings was investigated from a physiological and biochemical point of view. For this purpose, a completely randomized experiment was designed where the treatments included control (without stimulants and normal gravity), melatonin (100 μM), chitosan (230 M), microgravity, microgravity + melatonin, and microgravity + chitosan. The results disclosed that the microgravity significantly impaired the plant growth and morphology, while exogenous application of melatonin and chitosan improved the plant growth parameters under stress conditions. Under microgravity, there was a reduction of 46.15% in shoot length (4.9 mm) and 41.44% in root length (4.7 mm) compared with the control (9.1 mm; 8.03 mm), respectively. Clinorotation led to a marked increment in the enzymes activity, wherein the POD, SOD and CAT activities increased by 75.13%, 72.67%, and 53.42%, respectively, compared with the control seedlings. In addition, supply of these two stimulants strengthened the scavenging of radial oxygen species and helped the plant to tolerate stress conditions, by activated the enzymatic and non-enzymatic systems. These results can pave the road for more studies and broad application of biological stimuli to overcome the space harsh environmental conditions by plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Enhancer of Zeste Homologue 2 (EZH2) is part of the Polycomb Repressor Complex 2, which promotes trimethylation of lysine 27 on histone 3 (H3K27me3) and genes repression. EZH2 is overexpressed in many cancers and studies in mice attributed both pro-oncogenic and tumor suppressive functions to EZH2 in pancreatic ductal adenocarcinoma (PDAC). EZH2 deletion enhances de novo KRAS-driven neoplasia following pancreatic injury, while increased EZH2 expression in PDAC patients is correlated to poor prognosis, suggesting a context-dependant effect for EZH2 in PDAC progression. In this study, we examined EZH2 in pre- and early neoplastic stages of PDAC. Using an inducible model to delete the SET domain of EZH2 in adult acinar cells (EZH2∆SET), we showed loss of EZH2 activity did not prevent acinar cell regeneration in the absence of oncogenic KRAS (KRASG12D), nor increase PanIN formation following KRASG12D activation in adult mice. Loss of EZH2 did reduce recruitment of inflammatory cells and, when combined with a more aggressive PDAC model, promoted widespread PDAC progression and remodeling of the tumor microenvironment. This study suggests expression of EZH2 in adult acinar cells restricts PDAC initiation and progression by affecting both the tumour microenvironment and acinar cell differentiation.

Background & Aims: The fundamental biology of pancreatic ductal adenocarcinoma has been greatly impacted by the characterization of genetically engineered mouse models that allow temporal and spatial activation of oncogenic KRAS (KRAS G12D ). One of the most commonly used models involves targeted insertion of a cre-recombinase into the Ptf1a gene. However, this approach disrupts the Ptf1a gene, resulting in haploinsufficiency that likely affects sensitivity to oncogenic KRAS (KRAS G12D ). This study aims to determine if Ptf1a haploinsufficiency affected the acinar cell response to KRAS G12D before and after induction of pancreatic injury., Methods: We performed morphological and molecular analysis of 3 genetically engineered mouse models that express a tamoxifen-inducible cre-recombinase to activate Kras G12D in acinar cells of the pancreas. The cre-recombinase was targeted to the acinar-specific transcription factor genes, Ptf1a or Mist1/Bhlha15, or expressed within a BAC-derived Elastase transgene. Histological and RNA-seq analyses were used to delineate differences between the models., Results: Up to 2 months after tamoxifen induction of KRAS G12D , morphological changes were negligible. However, induction of pancreatic injury by cerulein resulted in widespread PanIN lesions in Ptf1a creERT pancreata within 7 days and maintained for at least 5 weeks post-injury, which was not seen in the models with 2 functional Ptf1a alleles. RNA-sequencing analysis prior to injury induction suggested Ptf1a creERT and Mist1 creERT mice have unique profiles of gene expression that predict a differential response to injury. Multiplex analysis of pancreatic tissue confirmed different inflammatory responses between the models., Conclusions: These findings suggest Ptf1a haploinsufficiency in Ptf1a creERT mouse models promotes KRAS G12D priming of genes for promotion of pancreatic ductal adenocarcinoma., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Infections may contribute to Alzheimer's disease (AD) risk. Limited evidence suggests Toxocara spp. infection/exposure could influence AD development., Methods: We investigated Toxocara seropositivity and AD in Iranian adults using a matched case-control study. Our sample included 90 AD cases and 91 healthy older adults. Anti-Toxocara immunoglobulin G (IgG) antibodies were assessed via enzyme-linked immunosorbent assay. We computed the odds ratios (ORs) and 95% confidence intervals (CIs) through univariable and multivariable analyses, adjusting for potential confounders., Results: There were 33/90 (36.67% [95% CI 26.75 to 47.48]) anti-Toxocara IgG seropositive individuals identified among the AD cases and 21/91 (23.07% [95% CI 14.89 to 33.09]) among the healthy controls. In univariable analysis, a significant association was identified between anti-Toxocara IgG seropositivity and AD (OR 1.93 [95% CI 1.01 to 3.69], p<0.001). Moreover, the association remained significant (OR 2.18 [95% CI 1.05 to 4.49], p<0.001) in multivariable analysis after adjustment for covariates. There was no association between anti-Toxocara IgG seropositivity and the severity of AD (OR 0.75 [95% CI 0.21 to 2.61], p=0.47)., Conclusions: Our findings indicated that Toxocara exposure/infection could be a potential risk factor for development of AD. To better understand a real causality between Toxocara exposure/infection and AD and related dementias, follow-up designed and adequately powered studies are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Despite the beneficial effects of antibiotics such as chloramphenicol (CAP), they exert some destructive impacts on human health. We designed an electrochemical sensor based on reduced graphene oxide (rGO)/Au/Co 2 CuS 4 nanohybrid for determination of CAP in food and biological samples. The Co 2 CuS 4 was synthesized from binuclear metal-organic framework (CoCu-BDC) through a two-step process. Nanohybrid was characterized by X-ray photoelectron spectroscopy and transmission electron microscopy. The rGO/Au/Co 2 CuS 4 provides more active sites and good electrical conductivity to reduce charge transfer resistance and improve the electrocatalytic activity for determination of CAP. The prepared sensor has a wide linear range from 7 to 141 nM with a limit of detection of 2.5 nM and a limit of quantification of 21.92 nM. It also provided high selectivity and repeatability with a relative standard deviation of 2.6%. Stability studies showed that the electrode has acceptable performance with efficiency of 95% after 33 days., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Few studies have investigated the potential predictive value of glycosylated hemoglobin A (HbA1c) and clinical outcomes in diabetic patients after percutaneous coronary intervention (PCI), and the results of the reports have often been inconclusive and contradictory. We have organized a study to investigate the relationship between HbA1c and the occurrence of major adverse cardiovascular events (MACE) in diabetic patients after PCI., Methods: This case-cohort study was conducted on 563 diabetic patients who underwent PCI. All studied patients had an HbA1c level measured within 24 h before angioplasty. All patients were followed for six months regarding the occurrence of MACE, and the HbA1c level was measured again at the end of the sixth month of follow-up. In the case of MACE, the subjects were considered the case group, and other non-MACE patients were included in the control group., Results: 505 patients remained in the study at the end of follow-up. MACE occurred in 23 (4.6%) patients during the first month and in 57 (11.3%) patients by the end of the sixth month. Baseline HbA1c was an independent predictor of MACE and mortality at the end of month-6 (P = 0.008 and 0.001, respectively)., Conclusions: The level of HbA1c at the time of admission has a significant predictive value for the occurrence of MACE in diabetic patients who undergo PCI. However, post-PCI glycemic control may not effectively reduce the risk of MACE in this population., Clinical Trial Registration: Not applicable., (© 2024. The Author(s).)

Purpose: PI4KA-related disorder is a highly clinically variable condition characterized by neurological (limb spasticity, developmental delay, intellectual disability, seizures, ataxia, nystagmus) and gastrointestinal (inflammatory bowel disease and multiple intestinal atresia) manifestations. Although features consistent with immunodeficiency (autoimmunity/autoinflammation and recurrent infections) have been reported in a subset of patients, the burden of B-cell deficiency and hypogammaglobulinemia has not been extensively investigated. We sought to describe the clinical presentation and manifestations of patients with PI4KA-related disorder and to investigate the metabolic consequences of biallelic PI4KA variants in B cells., Methods: Clinical data from patients with PI4KA variants were obtained. Multi-omics analyses combining transcriptome, proteome, lipidome and metabolome analyses in conjunction with functional assays were performed in EBV-transformed B cells., Results: Clinical and laboratory data of 13 patients were collected. Recurrent infections (7/13), autoimmune/autoinflammatory manifestations (5/13), B-cell deficiency (8/13) and hypogammaglobulinemia (8/13) were frequently observed. Patients' B cells frequently showed increased transitional and decreased switched memory B-cell subsets. Pathway analyses based on differentially expressed transcripts and proteins confirmed the central role of PI4KA in B cell differentiation with altered B-cell receptor (BCR) complex and signalling. By altering lipids production and tricarboxylic acid cycle regulation, and causing increased endoplasmic reticulum stress, biallelic PI4KA mutations disrupt B cell metabolism inducing mitochondrial dysfunction. As a result, B cells show hyperactive PI3K/mTOR pathway, increased autophagy and deranged cytoskeleton organization., Conclusion: By altering lipid metabolism and TCA cycle, impairing mitochondrial activity, hyperactivating mTOR pathway and increasing autophagy, PI4KA-related disorder causes a syndromic inborn error of immunity presenting with B-cell deficiency and hypogammaglobulinemia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chiral amino acids (AAs) are essential in metabolism and understanding physiological processes, and they could be used as biomarkers for the diagnosis of different diseases. In this study, chiral Cdots@Van were prepared by postmodifying an achiral Cdots core with vancomycin for recognizing and determining the enantiomeric excess (ee) of tyrosine (Tyr) enantiomers. The fluorescence response of Cdots@Van is based on an "on-off" strategy, with different quenching percentages for d- and l-tyrosine. Interestingly, the circular dichroism (CD) spectrum of Cdots@Van responded to only one form of Tyr enantiomer, specifically d-Tyr, and remained nearly unchanged upon the addition of l-Tyr. Quantum mechanical (QM) calculations were in excellent agreement with the experimental results, confirming the stronger binding affinity of Cdots@Van for d-Tyr compared to l-Tyr. We further investigated the chiral recognition ability of the interconnected vancomycin particles, which was synthesized using the EDC/NHS coupling reaction between vancomycin molecules without a Cdots core. Surprisingly, unlike free vancomycin molecules, interconnected vancomycin displayed an enantiomeric recognition ability by CD spectroscopy, similar to what was observed for Cdots@Van. Crucially, this chiral probe has been successfully utilized for cell imaging applications.

Background: Cardiovascular diseases remain a leading cause of global mortality, particularly among diabetic patients undergoing percutaneous coronary intervention (PCI). Chronic kidney disease (CKD) poses an additional risk in this population. Yet, its specific impact on major adverse cardiovascular events (MACEs), mortality, and triple vessel disease (TVD) post-PCI remains a topic of debate, specifically in patients with type 2 diabetes mellitus (T2DM)., Objective: This study aimed to examine the impact of renal function on MACE, mortality, and TVD among diabetic patients undergoing PCI., Methods: Diabetic patients undergoing PCI were analysed for renal function and outcomes. Participants were stratified by glomerular filtration rate (GFR). Logistic regression and receiver operating characteristic (ROC) analysis assessed associations and predictive capabilities., Results: A total of 505 patients enrolled in the study. A significant difference was observed regarding age, creatinine levels, and number of culprit vessels between diabetics with and without CKD. Severe CKD was associated with higher odds of 1-month mortality (OR: 15.694, p value <.001), 1-month MACE (OR: 7.734, p value <.001), and TVD (OR: 3.740, p value <.001). Patients with severe CKD also had significantly higher odds of 6-months mortality (OR: 12.192, p value <.001) and 6-months MACE (OR: 3.848, p value: .001). Moreover, GFR showed significant predictive accuracy for mortality at one- and six-months follow-up (AUC: 0.77 and 0.71, respectively)., Conclusions: Renal dysfunction, particularly severe CKD, significantly elevates risks of MACE, mortality, and TVD. Strategies to optimise renal function and tailor cardiovascular management could mitigate adverse outcomes in this high-risk population.

Purpose: To evaluate how risk factors impact success rates of initial probing and nasolacrimal duct (NLD) tube intubation in children over 18 months of age with congenital nasolacrimal duct obstruction (CNLDO)., Methods: This cohort study included 98 CNLDO patients aged 18 months to 10 years who underwent NLD probing with stent insertion. We employed the multivariate frailty model as our final model to conceptually elaborate on our correlated eye data, with the primary outcome measure evaluating the success rates of probing and tube intubation. Factors such as age, probing complexity, tube type, prior surgeries, and passive smoking were considered in the evaluation., Results: The study involved 98 patients (54 males, 44 females) with a mean age of 41.46 months and an average follow-up of 98.37 days (95 % CI 87.65-109.1). Out of the 110 eyes that underwent surgery, 13 (11.8 %) experienced failure while 97 (88.2 %) were censored. Kaplan-Meier analysis indicated significant differences in age category and probing (P-value = 0.03 and 0.006 respectively), but not tube type (P-value = 0.8). Multivariable analysis confirmed that older age and complex probing were associated with higher failure rates in CNLDO cases, with each monthly increase correlating to a two percent higher likelihood of intubation failure., Conclusions: Patient age and probing complexity influence CNLDO treatment, impacting surgical techniques and outcomes. Tube type, prior surgery, and passive smoking have no significant impact on treatment success., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

High-sensitivity nanoflow liquid chromatography (nLC) is seldom employed in untargeted metabolomics because current sample preparation techniques are inefficient at preventing nanocapillary column performance degradation. Here, we describe an nLC-based tandem mass spectrometry workflow that enables seamless joint analysis and integration of metabolomics (including lipidomics) and proteomics from the same samples without instrument duplication. This workflow is based on a robust solid-phase micro-extraction step for routine sample cleanup and bioactive molecule enrichment. Our method, termed proteomic and nanoflow metabolomic analysis (PANAMA), improves compound resolution and detection sensitivity without compromising the depth of coverage as compared with existing widely used analytical procedures. Notably, PANAMA can be applied to a broad array of specimens, including biofluids, cell lines, and tissue samples. It generates high-quality, information-rich metabolite-protein datasets while bypassing the need for specialized instrumentation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)