Assessing the stability and discriminative ability of radiomics features in the tumor microenvironment: Leveraging peri-tumoral regions in vestibular schwannoma.

PURPOSE: The tumor microenvironment (TME) plays a crucial role in tumor progression and treatment response. Radiomics offers a non-invasive approach to studying the TME by extracting quantitative features from medical images. In this study, we present a novel approach to assess the stability and discriminative ability of radiomics features in the TME of vestibular schwannoma (VS). METHODS: Magnetic Resonance Imaging (MRI) data from 242 VS patients were analyzed, including contrast-enhanced T1-weighted (ceT1) and high-resolution T2-weighted (hrT2) sequences. Radiomics features were extracted from concentric peri-tumoral regions of varying sizes. The intraclass correlation coefficient (ICC) was used to assess feature stability and discriminative ability, establishing quantile thresholds for ICCmin and ICCmax. RESULTS: The identified thresholds for ICCmin and ICCmax were 0.45 and 0.72, respectively. Features were classified into four categories: stable and discriminative (S-D), stable and non-discriminative (S-ND), unstable and discriminative (US-D), and unstable and non-discriminative (US-ND). Different feature groups exhibited varying proportions of S-D features across ceT1 and hrT2 sequences. The similarity of S-D features between ceT1 and hrT2 sequences was evaluated using Jaccard's index, with a value of 0.78 for all feature groups which is ranging from 0.68 (intensity features) to 1.00 (Neighbouring Gray Tone Difference Matrix (NGTDM) features). CONCLUSIONS: This study provides a framework for identifying stable and discriminative radiomics features in the TME, which could serve as potential biomarkers or predictors of patient outcomes, ultimately improving the management of VS patients.

AutoCorNN: An Unsupervised Physics-Aware Deep Learning Model for Geometric Distortion Correction of Brain MRI Images Towards MR-Only Stereotactic Radiosurgery.

Geometric distortions in brain MRI images arising from susceptibility artifacts at air-tissue interfaces pose a significant challenge for high-precision radiation therapy modalities like stereotactic radiosurgery, necessitating sub-millimeter accuracy. To achieve this goal, we developed AutoCorNN, an unsupervised physics-aware deep-learning model for correcting geometric distortions. Two publicly available datasets, the MPI-Leipzig Mind-Brain-Body with 318 subjects, and the Vestibular Schwannoma-SEG dataset, encompassing 242 patients were utilized. AutoCorNN integrates two 2D convolutional encoder-decoder neural networks with the forward physical model of MRI signal generation to predict undistorted MR and field map images from distorted MR input. The network is trained in an unsupervised manner by minimizing the mean absolute error between the measured and estimated k-space data, without requiring ground truth images during training or deployment. The model was evaluated on vestibular schwannoma cases. AutoCorNN achieved a peak signal-to-noise ratio (PSNR) of 41.35 ± 0.02 dB, a root mean square error (RMSE) of 0.02 ± 0.003, and a structural similarity index (SSIM) of 0.99 ± 0.02 outperforming uncorrected and B0-mapping correction methods. Geometric distortions of about 1.6 mm were observed at the air-tissue interfaces at the air canal and nasal cavity borders. Geometrically, distortion correction increased the target volume from 3.12 ± 0.52 cc to 3.84 ± 0.54 cc. Dosimetrically, AutoCorNN improved target coverage (0.96 ± 0.01 to 0.97 ± 0.02), conformity index (0.92 ± 0.03 to 0.94 ± 0.03), and reduced dose gradients outside the target. AutoCorNN achieves accurate geometric distortion correction comparable to conventional iterative methods while offering substantial computational acceleration, enabling precise target delineation and conformal dose delivery for improved radiation therapy outcomes.

The Role of Calcium in Non-Invasively Imaging Breast Cancer: An Overview of Current and Modern Imaging Techniques.

The landscape of breast cancer diagnostics has significantly evolved over the past decade. With these changes, it is possible to provide a comprehensive assessment of both benign and malignant breast calcifications. The biochemistry of breast cancer and calcifications are thoroughly examined to describe the potential to characterize better different calcium salts composed of calcium carbonate, calcium oxalate, or calcium hydroxyapatite and their associated prognostic implications. Conventional mammographic imaging techniques are compared to available ones, including breast tomosynthesis and contrast-enhanced mammography. Additional methods in computed tomography and magnetic resonance imaging are discussed. The concept of using magnetic resonance imaging particularly magnetic susceptibility to characterize the biochemical characteristics of calcifications is described. As we know magnetic resonance imaging is safe and there is no ionization radiation. Experimental findings through magnetic resonance susceptibility imaging techniques are discussed to illustrate the potential for integrating this technique to provide a quantitative assessment of magnetic susceptibility. Under the right magnetic resonance imaging conditions, a distinct phase variability was isolated amongst different types of calcium salts.

Development of a multi-purpose quality control phantom for MRI-based treatment planning in high-dose-rate brachytherapy of cervical cancer.

Purpose: Suitable commissioning and quality control (QC) tests for high-dose-rate brachytherapy (HDR-BT) is necessary to ensure dosimetric and geometric accuracy of the treatment. This study aimed to present the methodology of developing a novel multi-purpose QC phantom (AQuA-BT) and examples of its' application in 3D image-based (particularly magnetic resonance imaging [MRI]-based) planning for cervix BT. Material and methods: Design criteria led to a phantom with sufficient size waterproof box for dosimetry and capability for inserting other components inside the phantom for: (A) Validating dose calculation algorithms in treatment planning systems (TPSs) using a small-volume ionization chamber; (B) Testing volume calculation accuracy in TPSs for bladder, rectum, and sigmoid organs at risk (OARs) constructed by 3D printing; (C) Quantification of MRI distortions using 17 semi-elliptical plates with 4,317 control points to mimic a realistic female's pelvis size; and (D) Quantification of image distortions and artifacts induced by MRI-compatible applicators using a specific radial fiducial marker. The utility of the phantom was tested in various QC procedures. Results: The phantom was successfully implemented for examples of intended QC procedures. The maximum deviation between the absorbed doses to water assessed with our phantom and those calculated by SagiPlan TPS was 1.7%. The mean discrepancy in volumes of TPS-calculated OARs was 1.1%. The differences between known distances within the phantom on MR imaging were within 0.7 mm compared with computed tomography. Conclusions: This phantom is a promising useful tool for dosimetric and geometric quality assurance (QA) in MRI-based cervix BT.

Worldwide prevalence of human papillomavirus among pregnant women: A systematic review and meta-analysis.

Human papillomavirus (HPV) is the causative agent of cervical cancer and a suspected agent for ovarian and endometrial cancers in women. It is associated with adverse outcomes during pregnancy. To date, there is no estimate of the prevalence of HPV infection in pregnant women at the regional and global levels. This study evaluated the global prevalence of HPV infection based on all observational studies that had reported the prevalence of HPV among pregnant women between January 1980 and December 2021 in PubMed/MEDLINE, Scopus, Web of Science, Embase, and SciELO databases. We utilised a random-effect model to determine the global prevalence and related risk factors of HPV infection. Between-studies heterogeneity was assessed using I2 statistic. Moreover, subgroup and meta-regression analyses were employed to assess the source of heterogeneity and the relationship between HPV prevalence and socio-demographic factors, respectively. Among 144 eligible studies comprising 189 datasets, the overall prevalence rates of HPV at the 95% confidence interval (CI) were estimated as 30.38% (26.88%-33.99%), 17.81% (9.81%-27.46%), 32.1% (25.09%-39.67%), 2.26% (0.1%-8.08%) and 25.5% (23.3%-27.8%) in cervico-vaginal, placenta, serum, amniotic fluid and urine samples, respectively. The highest prevalence rates were estimated for countries in the African region, while countries in the European and Eastern Mediterranean regions showed the lowest prevalence rates. HPV-16 and -18 were the most prevalent isolated strains. The pregnant women living with HIV and those with pregnancy disorders had significantly higher prevalence rates than general pregnant women (p < 0.05). The younger ages for first intercourse and pregnancy, multiple lifetime sexual partners, and lower education levels were primary risk factors for HPV infection. In conclusion, although the overall HPV prevalence varied markedly based on sampling sites and geographical locations, the highest prevalence rates were observed in less-developed countries. Our findings imply that implementing behavioural and therapeutic interventions as well as vaccination programs are crucial to prevent and reduce the current burden of HPV infection among pregnant women.

Effects of Melatonin on Cardiac Injury and Inflammatory Biomarkers in Patients Undergoing Coronary Artery Bypass Graft Surgery: a Meta-analysis.

INTRODUCTION: The antiinflammatory and antioxidative effects of melatonin have been established in recent years. Several studies indicate that oxidative stress and inflammation are key drivers of post-coronary artery bypass graft (CABG) surgery complications. In the present study, we aimed to investigate the effects of melatonin on cardiac injury and inflammatory biomarkers in CABG candidates. METHODS: Embase, Medline/PubMed, Web of Science, Scopus, and the Cochrane library were searched up to 5 June 2022. All randomized controlled trials examining cardiac injury and inflammatory biomarkers of CABG patients who received melatonin were included. The random-effects model was utilized to perform the analysis. RESULTS: A total of 947 citations were retrieved through database searches. Finally, five articles (six trials with 342 patients) were included after the screening. Melatonin supplementation led to a significant reduction in cardiac troponin I (CTnI) [weighted mean difference(WMD): -2.28 ng/ml; 95% CI -2.87, -1.69; P < 0.01; I2: 91.25%] and high sensitivity-C reactive protein (hs-CRP) levels (WMD: -0.62 mg/L; 95% CI -0.73, -0.5; P < 0.01; I2: 99.98%) in patients undergoing CABG surgery. We found a nonsignificant decrease in creatine kinase isoenzyme muscle/brain (CK-MB) levels (WMD: -2.87 ng/ml; 95% CI -5.97, 0.23; P = 0.07; I2: 99.98%) after melatonin supplementation. No publication bias was found according to Egger's test. CONCLUSION: Melatonin supplementation may be useful in reducing cardiac injury and inflammatory biomarkers in CABG candidates. Future studies should investigate the clinical significance of these findings.

Population-based pattern of medication use and prevalence of polypharmacy among patients with cardiovascular diseases: results of the Pars cohort study from Iran.

BACKGROUND: Polypharmacy in patients with cardiovascular diseases (CVDs) has been linked to several adverse outcomes. This study aimed to investigate the pattern of medication use and prevalence of polypharmacy among CVDs patients in Iran. METHOD: We used the baseline data of the Pars cohort study (PCS). The participants were asked to bring their medication bags; then, the medications were classified using the Anatomical Therapeutic Chemical classification. Polypharmacy was defined as using five or more medications concurrently. Poisson regression modeling was applied. The adjusted prevalence ratios (PR) and its 95% confidence interval (CI) were estimated. RESULTS: Totally, 9262 participants were enrolled in the PCS, of whom 961 had CVDs. The prevalence of polypharmacy in participants with and without CVDs was 38.9% and 7.1%, respectively. The highest prevalence of polypharmacy (51.5%) was among obese patients. Abnormal waist-hip ratio (PR: 2.79; 95% CI 1.57-4.94), high socioeconomic status (PR: 1.65; 95% CI 1.07-2.54), tobacco-smoking (PR: 1.35; 95% CI 1.00-1.81), patients with more than three co-morbidities (PR: 1.41; 95% CI 1.30-1.53), high physical activity (PR: 0.66; 95% CI 0.45-0.95), use of opiate ever (PR: 0.46; 95% CI 0.26-0.82), and healthy overweight subjects (PR: 0.22; 95% CI 0.12-0.39) were associated with polypharmacy. Cardiovascular drugs (76.1%), drugs acting on blood and blood-forming organs (50.4%), and alimentary tract and metabolism drugs (33.9%) were the most frequently used drugs. Agents acting on the renin-angiotensin system were the mostly used cardiovascular system drugs among men and those above 60 years old, while beta-blocking agents were mostly prevalent among cardiovascular system drugs in women with CVDs. CONCLUSION: Given the high prevalence of polypharmacy among CVDs patients, and subsequent complications, programs to educate both physicians and patients to prevent this issue is crucial.

Human Papillomavirus Infection during Pregnancy and Childhood: A Comprehensive Review.

Human papillomavirus (HPV), the most prevalent sexually transmitted disease worldwide, is the causative agent for several genital and oropharyngeal cancers and a suspected agent for many malignancies. HPV is associated with several adverse health outcomes during pregnancy. Infants are also at risk of HPV infection via different transmission routes: vertically from an infected mother and horizontally through sexual or non-sexual contact with infected individuals. Several HPV manifestations have been identified during childhood, ranging from common skin infections to severe complications such as juvenile recurrent respiratory papillomatosis. This review aims to provide a comprehensive overview of the epidemiology, manifestations, and treatment strategies of HPV infection during pregnancy and childhood. Moreover, we underline the role of vaccination in preventing complications.

The Role of Genomics and Proteomics in Lung Cancer Early Detection and Treatment.

Lung cancer is the leading cause of cancer-related death worldwide, with non-small-cell lung cancer (NSCLC) being the primary type. Unfortunately, it is often diagnosed at advanced stages, when therapy leaves patients with a dismal prognosis. Despite the advances in genomics and proteomics in the past decade, leading to progress in developing tools for early diagnosis, targeted therapies have shown promising results; however, the 5-year survival of NSCLC patients is only about 15%. Low-dose computed tomography or chest X-ray are the main types of screening tools. Lung cancer patients without specific, actionable mutations are currently treated with conventional therapies, such as platinum-based chemotherapy; however, resistances and relapses often occur in these patients. More noninvasive, inexpensive, and safer diagnostic methods based on novel biomarkers for NSCLC are of paramount importance. In the current review, we summarize genomic and proteomic biomarkers utilized for the early detection and treatment of NSCLC. We further discuss future opportunities to improve biomarkers for early detection and the effective treatment of NSCLC.

The future of MRI in radiation therapy: Challenges and opportunities for the MR community.

Radiation therapy is a major component of cancer treatment pathways worldwide. The main aim of this treatment is to achieve tumor control through the delivery of ionizing radiation while preserving healthy tissues for minimal radiation toxicity. Because radiation therapy relies on accurate localization of the target and surrounding tissues, imaging plays a crucial role throughout the treatment chain. In the treatment planning phase, radiological images are essential for defining target volumes and organs-at-risk, as well as providing elemental composition (e.g., electron density) information for radiation dose calculations. At treatment, onboard imaging informs patient setup and could be used to guide radiation dose placement for sites affected by motion. Imaging is also an important tool for treatment response assessment and treatment plan adaptation. MRI, with its excellent soft tissue contrast and capacity to probe functional tissue properties, holds great untapped potential for transforming treatment paradigms in radiation therapy. The MR in Radiation Therapy ISMRM Study Group was established to provide a forum within the MR community to discuss the unmet needs and fuel opportunities for further advancement of MRI for radiation therapy applications. During the summer of 2021, the study group organized its first virtual workshop, attended by a diverse international group of clinicians, scientists, and clinical physicists, to explore our predictions for the future of MRI in radiation therapy for the next 25 years. This article reviews the main findings from the event and considers the opportunities and challenges of reaching our vision for the future in this expanding field.

The incidence and features of Delphian lymph node involvement in patients with papillary thyroid carcinoma.

INTRODUCTION: In papillary thyroid cancer patients, the extent of dissection is still a matter of debate. Evaluating Delphian lymph nodes (DLNs) during the surgery has been speculated as a valuable tool to determine the extent of dissection. Herein, we aimed to evaluate the incidence and features of DLNs involvement in patients with papillary thyroid carcinoma. METHOD: We conducted this cross-sectional study among surgical cases of papillary thyroid cancer. Patients were divided based on their DLNs involvement status. Their age, gender, location of the mass, lymphatic involvement, tumor size, tumor characteristics, pathology report, and operation note features were compared between the two groups. Definitive pathology slides of the patients were evaluated regarding DLN features. RESULTS: Of the 61 patients (mean age: 38.2 ± 12.0), 45 (73.8%) were females. In 13 (21.3%) patients, DLNs involvement was reported. A statistically significant relationship was noted between DLNs involvement and other lymph nodes' involvement on the same side of the mass (P < 0.001), the opposite side (P = 0.041), and also central lymph nodes (P < 0.001). Vascular invasion was also significantly higher among patients with DLNs involvement (P = 0.012). CONCLUSION: Since DLNs involvement is significantly associated with extensive nodal involvement, intraoperative evaluation of DLNs is recommended to establish the extent to which dissection should be performed.

A novel role for aspirin in enhancing the reprogramming function of miR-302/367 cluster and breast tumor suppression.

Recent studies have provided evidence for tumor suppressive function of the embryonic stem cell-specific miR-302/367 cluster through induction of a reprogramming process. Aspirin has been found to induce reprogramming factors of mesenchymal-to-epithelial transition in breast cancer cells. Therefore, we aimed to investigate whether overexpression of miR-302/367 cluster and aspirin treatment cooperate in the induction of reprogramming and tumor suppression in breast cancer cells. MDA-MB-231 and SK-BR-3 human breast cancer cell lines were transfected with a miR-302/367 expressing vector and treated with aspirin. The cells were evaluated for indices of apoptosis, proliferation, migration, and invasion. In both cell lines, treatment of miR-302/367-transfected cells with aspirin upregulated expression of some main pluripotency factors such as OCT4, SOX2, NANOG, and KLF4, and downregulated expression of some invasion and angiogenesis markers at gene and protein levels. Aspirin increased the apoptotic rate in both cell lines transfected with miR-302/367. Both miR-302/367 and aspirin upregulated the expression of FOXD3 protein which is a known inducer of OCT4 and NANOG. Our results demonstrate that aspirin can enhance miR-302/367-induced reprogramming of breast cancer cells possibly through upregulation of FOXD3 expression. This can further augment the reversal of epithelial-mesenchymal transition and inhibits migration, invasion, and angiogenic signaling in breast cancer cells reprogrammed by miR-302/367. Therefore, aspirin may serve as a useful adjuvant for reprogramming of cancer cells.

Potential of four definitions of metabolic syndrome to discriminate individuals with different 10-year cardiovascular disease risk scores: a cross-sectional analysis of an Iranian cohort.

OBJECTIVE: We aimed to reveal the potential of four different metabolic syndrome (Mets) definitions to differentiate subjects according to 10-year risk of cardiovascular disease. DESIGN: A cross-sectional analysis of a prospective cohort. SETTING: This study used baseline data from the Shiraz Heart Study, a prospective cohort study in Shiraz, Iran. Participants were screened against Mets definitions including modified WHO, National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), American Heart Association (AHA) and International Diabetes Federation (IDF). Also, Framingham risk score (FRS) and atherosclerotic cardiovascular disease (ASCVD) risk score were determined for each participant. PARTICIPANTS: A total number of 7225 participants of both genders entered the study. They were selected through defined family physician centres in different geographical areas. Urban residents with no migration plan were included. Those who were far from study centres or with disabilities that made them incapable to cooperate were excluded. RESULTS: Participants were 47.68% (N=3445) male with the mean age of 52.13±8.00 years. The number of subjects with Mets identified by WHO was the lowest (N=1676), while the percentage of subjects with high risk score was the highest, 17.1% (N=282) in FRS and 9.8% (N=162) in ASCVD risk score. There were statistically significant differences in the mean risk scores between participants with and without Mets according to AHA, WHO and NCEP ATP III definitions (p<0.001). In IDF definition, the risk scores of subjects with Mets were not statistically different compared with peers without Mets, neither based on FRS (p=0.247) nor ASCVD risk score (p=0.193). CONCLUSIONS: IDF was not the appropriate definition for discrimination of subjects with Mets and/or those at high risk of future cardiovascular events. AHA, WHO and NCEP ATP III definitions were effective to discriminate subjects with Mets from peers without Mets.

Cardiovascular Complications of SARS-CoV-2 Vaccines: An Overview.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the deadly disease known as coronavirus disease 2019 (COVID-19) that has reached pandemic proportions. Currently, there is no definitive treatment for COVID-19, although many vaccines have been developed. The World Health Organization has approved the safety and efficacy of the AstraZeneca/Oxford, Johnson and Johnson/Janssen (JnJ), Moderna, Pfizer/BioNTech, Sinopharm, and Sinovac vaccines so far. The approved formulations of AstraZeneca, JnJ, and Gam-COVID-vac (Sputnik V) contain DNA delivered within non-replicating recombinant adenovirus vector-based systems, while the Pfizer and Moderna vaccines utilize mRNA technology and lipid nanoparticle delivery systems. All of these vaccines encode production of the SARS-CoV-2 spike (S) protein, ultimately triggering immunity in the human body. COVID-19 causes several cardiovascular complications, such as arrhythmias, myocarditis, pericarditis, and venous thromboembolism. SARS-CoV-2 vaccines have been associated with rare, but sometimes fatal, cardiovascular side effects, which are the topics of this review. SARS-CoV-2 vaccines in general may cause thromboembolic events, such as cerebral vein thrombosis, and mRNA-based vaccines in particular may cause myocarditis/pericarditis, with the latter more likely to occur in younger adults after the second vaccination dose. Nevertheless, the advantages of these vaccines for ending the pandemic and/or decreasing the mortality rate outweigh any risk for the rare cardiovascular complications.

Toxocariasis-associated urinary system diseases: a systematic review of reported cases.

BACKGROUND: Toxocariasis is a neglected tropical disease caused by Toxocara canis and Toxocara cati. Toxocara species can involve many organs, such as the brain, heart and lungs, however, the urinary system involvement of toxocariasis is largely unknown. METHODS: We performed a systematic review to identify cases infected with urinary tract toxocariasis. RESULTS: We identified seven cases that were eligible to be reviewed. Among the included citations, four studies reported bladder involvement and three reported kidney involvement. Fever, urinary, and abdominal presentations were amongst the most important clinical symptoms. Eosinophilic cystitis and nephrotic syndrome were the most common diagnoses.. The treatment regimen included a combination of anthelmintic drugs and steroids. CONCLUSIONS: In cases of urinary tract presentations accompanied by eosinophilia or histopathologic findings suggestive of parasitic infection, toxocariasis should be included in the list of differential diagnoses, especially in endemic areas.

The Role of Dihydropyrimidine Dehydrogenase and Thymidylate Synthase Polymorphisms in Fluoropyrimidine-Based Cancer Chemotherapy in an Iranian Population.

BACKGROUND: The fluoropyrimidine drug 5-Fluorouracil (5-FU) and the prodrug capecitabine have been extensively used for treatment of many types of cancer including colorectal, gastric, head and neck. Approximately, 10 to 25% of patients suffer from severe fluoropyrimidine-induced toxicity. This may lead to dose reduction and treatment discontinuation. Pharmacogenetics research could be useful for the identification of predictive markers in chemotherapy treatment. The aim of the study was to investigate the role of five genetic polymorphisms within two genes (DPYD, TYMS) in toxicity and efficacy of fluoropyrimidine-based chemotherapy. METHODS: Total genomic DNA was extracted from 83 cancer patients treated with fluoropyrimidine-based chemotherapy. In this study, three polymorphisms were genotyped in dihydropyrimidine dehydrogenase gene c.1905+1 G>A (DPYD*2A; rs3918290), c.1679 T>G (I560S; DPYD*13; rs55886062), and c.2846A>T (D949V; rs67376798) and two polymorphisms, besides the Variable Number of Tandem Repeat (VNTR) polymorphism and 6-bp insertion/deletion polymorphism in thymidylate synthase gene. The analysis of polymorphisms for rs3918290, rs55886062, rs67376798 and 6-bp insertion/deletion in TYMS was done by Polymerase Chain Reaction-restriction Fragment Length Polymorphism (PCRRFLP) TYMS VNTR analysis. 5-FU-related toxicities such as anemia, febrile neutropenia, neurotoxicity, vomiting, nausea, and mucositis were evaluated according to NCI-CTC criteria version 4.0. T-test and chi-square were used and p-values less than 0.05 were considered statistically significant. RESULTS: DPYD gene polymorphisms were not observed in this study. The frequency of the TYMS +6 bp allele was 40.35% and the -6 bp allele was 59.65% in this study. The frequency of VNTR 2R allele was 48.75% and 3R allele was 51.15%. Toxicity grade II diarrhea, mucositis, nausea, vomiting, and neurotoxicity was 2.2, 24.1, 15.7, 6, and 51.8%, respectively. Thymidylate synthase ins/del polymorphisms were associated with increased grade III neurotoxicity (p=0.02). Furthermore, anemia grade III was significantly associated with 2R/2R genotype (0.009). CONCLUSION: Thymidylate synthase gene polymorphisms may play a key role in fluoropyrimidne -based chemotherapy. Although rare DPYD polymorphisms were not observed in our study, according to large population studies, DPYD gene polymorphisms could be used as a predictive biomarker for patient treatments.

Continuous growth phenomenon for direct synthesis of monodisperse water-soluble iron oxide nanoparticles with extraordinarily high relaxivity.

The direct synthesis of highly water-soluble nanoparticles has attracted intensive interest, but systematic size control has not been reported. Here, we developed a general method for synthesizing monodisperse water-soluble iron oxide nanoparticles with nanometer-scale size increments from 4 nm to 13 nm in a single reaction. Precise size control was achieved by continuous growth in an amphiphilic solvent, diethylene glycol (DEG), where the growth step was separated from the nucleation step by sequential addition of a reactant. There was only one reactant in the synthesis and no need for additional capping agents and reducing agents. This study reveals the "living growth" character of iron oxide nanoparticles synthesised in an amphiphilic solvent. The synthetic method shows high reproducibility. The as-prepared iron oxide nanoparticles are extremely water soluble without any surface modification. Surprisingly, the synthesized 9 nm iron oxide nanoparticles exhibit extremely high transversal and longitudinal relaxivities of 425 mM-1 s-1 and 32 mM-1 s-1 respectively, which is among the highest transversal relaxivity in the literature for sub-10 nm spherical nanoparticles. This study will not only shed light on the continuous growth phenomenon of iron oxide nanoparticles in an amphiphilic solvent, but could also stimulate the synthesis and application of iron oxide nanoparticles. The continuous growth method could be further extended to other materials for the controlled synthesis of water-soluble nanoparticles.

Ultrastructural and optical characteristics of cancer cells treated by a nanotechnology based chemo-photothermal therapy method.

The current chemotherapy method demonstrates the need for improvement in terms of efficacy and safety. Given the beneficiary effect of heat in combination with chemotherapy, the purpose of this study is to develop a multifunctional nanoplatform by co-incorporating gold nanoparticles (AuNPs) as photothermal agent and cisplatin as anticancer drug into alginate hydrogel (named as ACA) to enable concurrent thermo-chemotherapy. The in vitro cytotoxicity experiment showed that the as-developed nanocomplex was able to induce greater cytotoxicity in KB human nasopharyngeal cancer cells compared to free cisplatin at the same concentration. Moreover, the interaction of ACA and laser irradiation acted synergistically and resulted in higher cell death rate compared to separate application of photothermal therapy and chemotherapy. The micrograph of KB cells also revealed that ACA was able to selectively accumulate into the mitochondria, so that laser irradiation of KB cells pre-treated with ACA resulted in intensive morphological damages such as plasma membrane disruption, chromatin condensation, autophagic vacuoles formation and organelle degeneration. Moreover, the sign and magnitude of optical nonlinear refractive index measured by Z-scan technique was shown to be significantly altered in cells exposed to ACA with and without laser irradiation. Consequently, the nanocomplex developed herein could be a promising platform to combine photothermal therapy and chemotherapy effectively, thereby achieving synergistic therapeutic outcome.

Association of interleukin-1 gene polymorphism with risk of gastric and colorectal cancers in an Iranian population.

BACKGROUND: Chronic inflammation is associated with neoplasms and several types of cancer. Therefore, polymorphisms in the inflammation-related genes could modify the cancer susceptibility. OBJECTIVE: To investigate the associations between IL-1RN VNTR and rs419598 polymorphisms in IL-1 receptor antagonist (IL-1ra) and colorectal cancer (CRC) and gastric cancer (GC) in an Iranian population. METHODS: In this study, 126 cancer cases (91 CRC and 35 GC) and 97 healthy controls were included. Genotyping of IL-1RN VNTR and rs419598 was performed by PCR amplification and PCR-RFLP, respectively. Logistic regression was applied to identify the independent risk factors for colorectal and gastric cancers by computing the odds ratio (OR) and 95% confidence intervals (95% CI). All statistical analyses were performed using the SPSS statistical software. RESULTS: There were significant differences between cancer groups and control group concerning the frequency of A1/A2 genotypes in IL-1RN VNTR polymorphism. The carrier status of IL-1RN* 2 allele was associated with increased risk of CRC (p = 0.0003; OR = 0.02; 95% CI: 0.491-0.85) and GC (p = 0.0006; OR = 0.106; 95% CI: 0.321-0.035). Also, the homozygous ILRN *2/*2 genotype was associated with increased risk of gastric cancer (p = 0.04; OR = 0.133; 95% CI: 0.020-0.908). There was no association between different alleles of rs419598 and CRC and GC. CONCLUSION: This study demonstrates an association between the carrier status of IL-1RN* 2 and CRC and GC in an Iranian population.

Evaluation of interleukin 12 and CD56+ lymphocyte cells in pediatric hematopoietic stem cell transplantation for early diagnosis of acute graft versus host disease.

The present study tried to explain CD56+ lymphocyte cells activities and possible prognostic role of these cells in Graft-Versus-Host-Disease (GVHD). The role of IL-12 activation and function is of interest in this study. Peripheral blood samples of 51 Hematopoietic Stem Cell Transplantation (HSCT) recipients collected at before (day -8) and after (days 7 and 14). PBMC were collected by Ficoll separation and analyzed by Flow Cytometry using triple antibody (CD45-PerCP, CD56-FITC, and CD69-PE staining and control antibody. Levels of the cytokine IL-12 in the patient's serum were evaluated by ELISA. Percentage of CD56+ lymphocytes (CD56+bright) cells was significantly increased at day 14 in patients with acute GVHD and percentage of lymphocytes expressing CD69 was significantly increased at days 7 and 14 posts HSCT in patients with acute GVHD in comparison to those in non-GVHD patients. Baseline serum IL-12 levels (pre-HSCT, day -8) were significantly higher in those HSCT recipients who did not develop GVHD. This study showed that post-transplant CD56+ lymphocytes and pre-transplant serum levels of IL-12 play significant roles in the induction of and protection against GVHD, respectively. The increase in the percentage of CD69+ cells indicates the activation of lymphocyte in acute GVHD group.