Molecular imaging using positron emission tomography in gastrointestinal malignancy

Positron Emission Tomography (PET) with 18F-FDG has emerged as a powerful tool in oncology. Furthermore, recent advent of PET/CT and novel tracers are continually expanding its role. This thesis investigates its application in two solid cancer models. In the diagnosing of primary pancreatic cancer, 18F-FDG PET/CT was shown to be more accurate than conventional CT. It did not add information to locoregional staging of disease but impacted management of patients with potentially operable tumours, by accurately confirming the presence / absence of metastases. In the pre-operative staging of patients with colorectal liver metastases (CLM), 18F- FDG PET/CT was also superior to CT in assessing extrahepatic disease, where it again impacted management. The accuracy of detecting hepatic disease was similar for both. Compared to PET alone, PET/CT improved the accuracy of lesions localization and interpretation. Next, the feasibility of imaging with the novel thymidine analogue tracer 18F-FLT was investigated. Overall, 18F-FLT PET was less accurate than 18F-FDG in detecting lesions in both cancer types, thus suggesting it to be an unsuitable tracer for routine diagnosis and staging. In the cohort of pancreatic cancer patients, 18F-FLT uptake (SUVs) were found to strongly correlate with the immunohistochemical proliferation marker, Ki-67 antigen. This supported 18F-FLT‟s potential role as a surrogate marker of proliferation. The prognostic implications of these require further investigation. Finally, an in vitro model was use to examine early changes in 18F-FLT uptake in response to treatment with cytotoxics. At 2 hours following pulse treatment with 5-fluorouracil, (and before changes in cell numbers and cell cycle phase were seen), a dose dependent increase in 18F-FLT uptake was seen. No change was observed with 18F-FDG nor following Cisplatin treatment. This adaptive response may have a role as an early predictor of response to 5-FU (and potentially other antimetabolites), which requires further investigation

Spatial analysis of skin cancer incidence in Iran

Skin cancer is one of the most common cancers worldwide, including in Iran. Variations in its incidence rate among geographical areas are due to various contributing factors. Since there has been a lack of studies on this topic in our country, the present spatial analysis of skin cancer incidence in Iran in 2009 was conducted using data from the cancer registry system for the country. The reported incidences of the disease were standardized on the basis of the World Health Organization population and the direct method. Then the data were inserted into the GIS software, and finally, using the analysis of hot spots (Getis-Ord Gi), high-risk areas were drawn. Provinces that were 1.9 SD higher or lower than the national average were considered hot spots or cold spots, with significance at the level of 0.05. In 2009, a total of 9,964 cases of skin cancer occurred, 3,696 in women and 6,268 in men (standardized incidence rates of 15.8 and 22.6, respectively). The results of the study showed that in men and women, the disease demonstrated high incidence in the central provinces and desert regions. In women, Yazd Province and in men, Qom Province had significant hot spots (p < 0.05). While Isfahan, Markazi, Tehran and Kurdistan provinces were expected to be hot spots, the differences from the national average were not significant at the 0.05 level. As well, the provinces of Sistan Va Baluchistan, Kerman, and Hormozgan were identified as cold or low-risk disease regions (p < 0.05). The central provinces of the country due to hot weather conditions, more solar radiation, and closer vicinity to the central desert of Iran demonstrated higher incidence rates for skin cancer, so further epidemiological studies into the etiology and early detection are essential in these areas. © 2016, Asian Pacific Journal of Cancer Prevention

Spatial analysis of colorectal cancer in Iran

Colorectal cancer is one of the most common cancers. Due to demographic changes, it is predicted that the incidence of this cancer will increase. Variations of its incidence rate among geographical areas are due to various contributing factors. Since there have been a lack of studies on this topic in our country, the present assessment of spatial patterns of colorectal cancer incidence in Iran was performed. In this ecological study, the new cases of colon cancer were extracted from Cancer Registry Center report of the Health Deputy of Iran in 2009. The reported incidences of the disease were standardized on the basis of the World Health Organization population and the direct method. Then the data were inserted into the GIS software, and finally, using the analysis of hot spots (Getis-Ord Gi) high-risk areas were drawn. Provinces that are higher or lower than the national average (1.9 SD) were considered hot spots or cold spots, significant at the level of 0.05. A total of 6,210 cases of colorectal cancer were registered in Iran in 2009, of which 3,727 were in men and 2,783 in women (age-standardized rates of 11.3 and 10.9 per 100,000 population, respectively). The results showed that in central and northern Iran including Isfahan, Qom, Tehran, Qazvin and Mazandaran significant hot spots in men were present (p < 0.05). In women also we have high incidence in northern and central states: Mazandaran province (p < 0.01) and the province of Tehran (p < 0.05) had higher incidences than the national average and were apparent as significant hot spots. Analysis of the spatial distribution of colorectal cancer showed significant differences between different areas pointing to the necessity for further epidemiological studies into the etiology and early detection. © 2016, Asian Pacific Journal of Cancer Prevention

Orientability and energy minimization in liquid crystal models

Uniaxial nematic liquid crystals are modelled in the Oseen-Frank theory through a unit vector field $n$. This theory has the apparent drawback that it does not respect the head-to-tail symmetry in which $n$ should be equivalent to -$n$. This symmetry is preserved in the constrained Landau-de Gennes theory that works with the tensor $Q=s\big(n\otimes n- \frac{1}{3} Id\big)$.We study the differences and the overlaps between the two theories. These depend on the regularity class used as well as on the topology of the underlying domain. We show that for simply-connected domains and in the natural energy class $W^{1,2}$ the two theories coincide, but otherwise there can be differences between the two theories, which we identify. In the case of planar domains we completely characterise the instances in which the predictions of the constrained Landau-de Gennes theory differ from those of the Oseen-Frank theory

A Roadmap for the Production of a GMP-Compatible Cell Bank of Allogeneic Bone Marrow-Derived Clonal Mesenchymal Stromal Cells for Cell Therapy Applications

Background: Allogeneic mesenchymal stromal cells (MSCs) have been used extensively in various clinical trials. Nevertheless, there are concerns about their efficacy, attributed mainly to the heterogeneity of the applied populations. Therefore, producing a consistent population of MSCs is crucial to improve their therapeutic efficacy. This study presents a good manufacturing practice (GMP)-compatible and cost-effective protocol for manufacturing, banking, and lot-release of a homogeneous population of human bone marrow-derived clonal MSCs (cMSCs). Methods: Here, cMSCs were isolated based on the subfractionation culturing method. Afterward, isolated clones that could reproduce up to passage three were stored as the seed stock. To select proliferative clones, we used an innovative, cost-effective screening strategy based on lengthy serial passaging. Finally, the selected clones re-cultured from the seed stock to establish the following four-tired cell banking system: initial, master, working, and end of product cell banks (ICB, MCB, WCB, and EoPCB). Results: Through a rigorous screening strategy, three clones were selected from a total of 21 clones that were stored during the clonal isolation process. The selected clones met the identity, quality, and safety assessments criteria. The validated clones were stored in the four-tiered cell bank system under GMP conditions, and certificates of analysis were provided for the three-individual ready-to-release batches. Finally, a stability study validated the EoPCB, release, and transport process of the frozen final products. Conclusion: Collectively, this study presents a technical and translational overview of a GMP-compatible cMSCs manufacturing technology that could lead to the development of similar products for potential therapeutic applications. Graphical Abstract: [Figure not available: see fulltext.

Improved X-ray computed tomography reconstruction of the largest fragment of the Antikythera Mechanism, an ancient Greek astronomical calculator

The Antikythera Mechanism is an extraordinarily complex ancient Greek astronomical calculating device whose mode of operation is now relatively well understood particularly since imaging studies in 2005 revealed gears and inscriptions which were previously illegible. Unfortunately, the highest resolution X-ray computed tomography image of the largest fragment had some errors which meant that the reconstructed images were not as clear as had been expected. Here, the original X-ray data have been reanalysed and reconstructed. The new X-ray computed tomography images have improved contrast and resolution, leading to better clarity and legibility. The improvement in image quality is characterised and some examples of writing on the Mechanism which can now be read with increased confidence are given

The effect of modern intensive monitoring in obstetrics on infant mortality and the incidence of hypoxia and acidosis

Peer Reviewe

Economic inequality in unmet refractive error need in deprived rural population of Iran

Purpose: To determine economic inequality in unmet refractive error (RE) need and its determinants in deprived rural population of Iran. Methods: In this population-based study, two villages were randomly selected from among underserved villages of Iran. After selecting the participants, optometric examinations, including uncorrected and corrected visual acuity and subjective and manifest refraction, were done for all the participants. Then, unmet need for glasses was determined. Concentration index (C) was used to assess inequality, and Oaxaca-Blinder decomposition method was applied to decompose the gap between the two groups based on the determinants. Results: Of 3851 samples, 3314 participated in the study (response rate = 86.05). The data of 3255 participants were used for analysis. The value of C and 95 confidence interval (CI) was-0.088 (-0.157 to-0.020), indicating a pro-poor inequality in unmet need. The prevalence (95 CI) of unmet need was 11.74 (9.25-14.22) in the poor and 6.51 (4.96-8.06) in the rich, with a gap of about 5 in favor of the rich (P < 0.001). A marked percentage of the gap was due to the explained portion (b = 5.73; P = 0.031). In the explained portion, the variable of economic status (b = 3.48; P = 0.004) and myopia (b = 0.88; P = 0.031) caused inequality in favor of the rich and against the poor, respectively. In the unexplained portion (b =-0.51; P = 0.372), the variables of education (P = 0.002) and place (P = 0.001) had statistically significant effects on inequality. Conclusions: There is a significant pro-poor economic inequality in the prevalence of unmet need in rural areas of Iran. Although part of this inequality is related to variables such as education and myopia, a major portion (two thirds) of this inequality may be due to the direct effect of economic inequality. © 2020 Journal of Current Ophthalmology | Published by Wolters Kluwer-Medknow

Phenotypic and Genotypic Characterization of ESBL-, AmpC-, and Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli Isolates

Objectives: Drug resistance among gram-negative bacteria is a worldwide challenge. Due to the importance of drug-resistant Klebsiella pneumoniae and Escherichia coli strains in hospital-acquired infections, we aimed to determine the phenotypic and genotypic characteristics of ESBL-, AmpC-, and carbapenemase-producing isolates obtained from hospitalized patients in Tehran and Ilam (Iran). Materials and Methods: In total, 90 K. pneumoniae isolates and 65 E. coli isolates were collected from various infections. Phenotypic identification of bacterial isolates was performed using standard methods. Phenotypic screening of ESBL, AmpC, and carbapenemase enzymes was carried out. Detection of ESBL, AmpC, and carbapenemase genes was also performed by the PCR method. Results: Phenotypic detection tests showed that 36 (40) K. pneumoniae and 23 (35.4) E. coli isolates were ESBL producers. Moreover, 18 (20) and 6 (9.2) K. pneumoniae and E. coli isolates were AmpC producers, respectively. Modified Hodge test results indicated that 39 (43.3) K. pneumoniae and 18 (27.7) E. coli isolates produced carbapenemase. Molecular tests showed that 40 of K. pneumoniae and 36.9 of E. coli isolates were ESBL positive. AmpC was detected in 24.4 and 13.8 of K. pneumoniae and E. coli isolates. Carbapenemase was detected in 34 (37.8) K. pneumoniae and 13 (20) E. coli isolates. -Conclusion: In this study, 3 K. pneumoniae isolates simultaneously carried ESBL, AmpC, and carbapenemase genes. Up-to-date strategies such as combination therapy or utilization of new antimicrobial agents might help to combat such drug-resistant organisms. © 2019 The Author(s) Published by S. Karger AG, Basel

Acinetobacter baumannii clonal lineages I and II harboring different carbapenem-hydrolyzing-β-lactamase genes are widespread among hospitalized burn patients in Tehran

The aim of this study was to analyze antimicrobial resistance patterns and their encoding genes and genotypic diversity of Acinetobacter baumannii isolated from burn patients in Tehran, Iran. The presence of extended-spectrum beta-lactamase- and blaOXA-encoding genes among 37 multidrug resistant (MDR) A. baumannii strains isolated from patients hospitalized in a teaching hospital in Tehran was evaluated. Susceptibility to 7 antibiotics was tested by disk agar diffusion and to polymyxin B and colistin was tested by E-test, according to CLSI guidelines. All isolates were then analyzed by PCR for the presence of blaIMP, blaVIM, blaSIM blaOXA-23, blaOXA-24, and blaOXA-58-like carbapenemase genes, and blaOXA-51-like, blaTEM, blaSHV, blaPER, blaVEB, and blaGIM genes. Genotyping of A. baumannii strains was performed by repetitive sequence-based (REP)-PCR and cluster analysis of REP-PCR profiles. A. baumannii isolates were assigned to international clones by multiplex PCR sequence group analysis. Twenty-five A. baumannii isolates were classified as MDR, and 12 were classified as extensively drug resistant. All isolates were susceptible to colistin and polymyxin B. Eighty-one percent of the isolates was resistant to imipenem or meropenem and harbored at least one or both of the blaOXA-23-like or blaOXA-24-like carbapenemase genes. Co-existence of different resistance genes was found among carbapenem-resistant isolates. Multiplex PCR sequence group analysis most commonly assigned A. baumannii isolates to international clones I (18/37; 48.6) and II (18/37; 48.6). An alarming increase in resistance to carbapenems and the spread of blaOXA-23-like and/or blaOXA-24-like carbapenemase genes was observed among A. baumannii strains belonging to clonal lineages I and II, isolated from burn patients in Tehran. © 2015 King Saud Bin Abdulaziz University for Health Sciences