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Purpose To assess the feasibility of luminal water imaging, a quantitative T2-based magnetic resonance (MR) imaging technique, for the detection and grading of prostate cancer (PCa). Materials and Methods Eighteen patients with biopsy-proven PCa provided informed consent to be included in this institutional human ethics board-approved prospective study between January 2015 and January 2016. Patients underwent 3.0-T MR imaging shortly before radical prostatectomy. T2 distributions were generated with a regularized non-negative least squares algorithm from multiecho spin-echo MR imaging data. From T2 distributions, maps of seven MR parameters, N comp , T2 short , T2 long , geometric mean T2 (gmT2), luminal water fraction (LWF), A short , and A long , were generated and compared with digitized images of hematoxylin-eosin-stained whole-mount histologic slices. A paired t test was used to determine significant differences between MR parameters in malignant and nonmalignant tissue. Correlation with Gleason score (GS) was evaluated with the Spearman rank correlation test. Diagnostic accuracy was evaluated by using logistic generalized linear mixed-effect models and receiver operating characteristic (ROC) analysis. Results The average values of four MR parameters (gmT2, A short , A long , and LWF) were significantly different between malignant and nonmalignant tissue. All MR parameters except for T2 long showed significant correlation (P < .05) with GS in the peripheral zone. The highest correlation with GS was obtained for LWF (-0.78 ± 0.11, P < .001). ROC analysis demonstrated high accuracy for tumor detection, with the highest area under the ROC curve obtained for LWF (0.97 in the peripheral zone and 0.98 in the transition zone). Conclusion Results of this pilot study demonstrated the feasibility of luminal water imaging in the detection and grading of PCa. A study with a larger cohort of patients and a broader range of GS is required to further evaluate this new technique in clinical settings. © RSNA, 2017.

Interleukin-1β (IL-1β) is known to trigger beta cell dysfunction in vitro and could potentially play a role during the pathogenesis of type 1 diabetes and type 2 diabetes. However, several clinical trials attempting to block IL-1β function have had minimal success. We therefore re-investigated local expression of IL-1β in human diabetic and non-diabetic pancreata. We obtained pancreatic tissue sections from the Network for Pancreatic Organ Donors with Diabetes (nPOD) including non-diabetic (n = 9), non-diabetic auto-antibody positive (AAb+, n = 5), type 1 diabetes (n = 6), and type 2 diabetes (n = 6) donors. Islets were systematically investigated for the presence of IL-1β mRNA by in situ hybridization and IL-1β protein by indirect immunofluorescence. We found that intra-islet IL-1β was produced at comparable level in both non-diabetic and diabetic donors. Interestingly, the main source for IL-1β was alpha cells but not beta cells. Our findings call into question the role of IL-1β in the diabetic pancreas as it has been proposed in previous literature. Additionally, our results regarding the localization of IL-1β should lead to further investigation into the role of IL-1β in the physiology of pancreatic alpha cells., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Phage therapy is an old method of combating bacterial pathogens that has recently been taken into consideration due to the alarming spread of antibiotic resistance. Escherichia coli O157:H7 is a foodborne pathogen that causes hemorrhagic colitis and life-threatening Hemolytic Uremic Syndrome (HUS). There are several studies on isolation of specific phages against E. coli O157:H7 and more than 60 specific phages have been published so far. Although in vitro experiments have been successful in elimination or reduction of E. coli O157:H7numbers, in vivo experiments have not been as promising. This may be due to escape of bacteria to locations where phages have difficulties to enter or due to the adverse conditions in the gastrointestinal tract that affect phage viability and proliferation. To get around the latter obstacle, an alternative phage delivery method such as polymer microencapsulation should be tried. While the present time results are not very encouraging the work should be continued as more efficient phage treatment regimens might be found in future., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Study Objective: The risk of airway collapse in patients undergoing deep sedation is a major concern. In this study, we compared the airway patency of deep sedation provided by propofol with the airway patency of deep sedation provided by dexmedetomidine in magnetic resonance imaging (MRI) procedures. This comparison was done using MRI static and dynamic images and comparing these images to baseline after sevoflurane induction., Design: After institutional review board approval, children who were scheduled for MRI procedures were given an inhalation induction, had intravenous access established, and were randomized to receive either dexmedetomidine 1-μg/kg load followed by 1-μg/(kg h) infusion or propofol infusion at 300 μg/(kg min) reduced to 250-μg/(kg min) infusion. MR images were then obtained. Airway patency and collapse were assessed at the level of the posterior midtongue in the axial and sagittal planes. The degree of airway collapse was assessed by determining the percent change in the airway caliber from its minimum to maximum value. After conclusion of the MRI procedure, the study patients were immediately observed by a blinded observer to determine their level of sedation according to the Ramsey sedation scale., Setting: MRI scanner at Women and Children's Hospital of Buffalo., Patients: Forty children between the ages of 3 and 7 years., Intervention: Comparison of the utilization of propofol against dexmedetomidine infusions for deep sedation to determine the degree of airway collapse., Measurements: Magnetic resonance images were then obtained using a 1.5-T GE Excite 12.0 scanner. Airway patency and collapse were assessed at the level of the posterior midtongue in the axial and sagittal planes. The degree of airway collapse was assessed by determining the percent change in the airway caliber from its minimum to maximum value. After conclusion of the MRI procedure, the study patients were immediately observed by a blinded observer to determine their level of sedation according to the Ramsey sedation scale., Main Results: Our study demonstrated no difference in airway collapse between dexmedetomidine-based deep sedation and propofol-based deep sedation following sevoflurane induction., Conclusion: In deep sedation, which is commonly associated with a loss of airway tone, it may not matter which of these intravenous study agents are used. Intravenous sedation with propofol or dexmedetomidine appears to produce the same effect on the pediatric airway., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Type 1 diabetes (T1D) is an autoimmune disease characterized by the loss of pancreatic beta cells in the islets of Langerhans. Although genetic predisposition plays an important role in T1D development, studies of identical twins suggest that environmental factors such as viruses and other pathogens may be critical triggers either through direct cytolytic effect and gradual beta cell destruction, or by bystander activation of the immune system. In addition, viruses may circumvent the host immune response and have the capacity to establish chronic lifelong infections. The association of various viral infections with the induction of T1D has been extensively studied at the serological and epidemiological level. However, there is still little evidence from studies of human pancreas to confirm their presence or a causal role in disease pathogenesis. In this review, we identify possible suspects for viral triggers of disease and explain their potential roles in the "viral paradigm" of T1D., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The Dark Triad (DT) describes a set of three closely related personality traits, Machiavellianism, narcissism, and psychopathy. The aim of this study was to examine the associations between DT traits, sleep disturbances, anxiety sensitivity and intolerance of uncertainty., Method: A total of 341 adults (M=29years) completed a series of questionnaires related to the DT traits, sleep disturbances, anxiety sensitivity, and intolerance of uncertainty., Results: A higher DT total score was associated with increased sleep disturbances, and higher scores for anxiety sensitivity and intolerance of uncertainty. In regression analyses Machiavellianism and psychopathy were predictors of sleep disturbances, anxiety sensitivity, and intolerance of uncertainty., Conclusions: Results indicate that specific DT traits, namely Machiavellianism and psychopathy, are associated with sleep disturbances, anxiety sensitivity and intolerance of uncertainty in young adults., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Statement of Problem: Impacts and accidents are considered as the main fac- tors in losing the teeth, so the analysis and design of the implants that they can be more resistant against impacts is very important. One of the important nu- merical methods having widespread application in various fields of engineering sciences is the finite element method. Among its wide applications, the study of distribution of power in complex structures can be noted., Objectives: The aim of this research was to assess the geometric effect and the type of implant thread on its performance; we also made an attempt to determine the created stress using finite element method., Materials and Methods: In this study, the three dimensional model of bone by using Cone Beam Computerized Tomography (CBCT) of the patient has been provided. The implants in this study are designed by Solid Works software. Loading is simulated in explicit dynamic, by struck of a rigid body with the speed of 1 mm/s to implant vertically and horizontally; and the maximum level of induced stress for the cortical and trabecular bone in the ANSYS Workbench software was calculated., Results: By considering the results of this study, it was identified that, among the designed samples, the maximum imposed stress in the cortical bone layer occurred in the first group (straight threads) and the maximum stress value in the trabecular bone layer and implant occurred in the second group (tapered threads)., Conclusions: Due to the limitations of this study, the implants with more depth thread, because of the increased contact surface of the implant with the bone, caused more stability; also, the implant with smaller thread and shorter pitch length caused more stress to the bone.

Background: The aim of this study was to compare the quality of life (QOL) of people infected with both hepatitis C virus (HCV) and human immunodeficiency virus (HIV). The study design was a cross sectional descriptive survey, using self administered questionnaires., Materials and Methods: A convenience sample of 242 patients (131 of them HIV/HCV), Iranian adults (aged 18-57) living with HIV/AIDS, was recruited from outpatient referring to Imam Khomeini Hospital behavioral counseling center in Tehran city, Iran. The instruments included the Multidimensional QOL HIV (MQoL HIV) and a demographic section., Results: The majority of the samples were male and single. The mean age was 36.52 years (standard deviation = 8.5). HIV mono infected patients reported higher scores in social support and physical functioning, but lower scores in physical health compared with HIV/HCV co infected individuals. There was no significant difference in overall MQOL HIV score between HIV and HIV/HCV patients., Conclusion: Future studies will need to explore the impact of HCV on HIV infected individuals' QOL.

Background: Middle cerebral artery (MCA) fenestration is a very rare anatomical variant of the MCA, incidentally found during magnetic resonance or computed tomography angiography. It has an incidence of 0.6%. Unlike fenestration of the posterior cerebral arterial circulation, fenestration of the anterior cerebral arterial circulation has not been well described., Methods: We present the rare case of a patient who was admitted for a ruptured aneurysm of the MCA arising at the site of the fenestration of the MCA and also an unruptured fusiform aneurysm of the right posterior communicating artery and a distal anterior cerebral artery (ACA) aneurysm., Results: The patient underwent craniotomy with microsurgical aneurysm clipping and the previously undiagnosed ruptured aneurysm, at the site of the fenestration of the MCA, arose immediately. Postoperatively, the patient awoke without a deficit. After treatment of postoperative bacterial meningitis, he was discharged on the 26(th) postoperative day in good condition without any neurologic deficit. Six months after the first surgery, he was operated for the distal azygos ACA aneurysm., Conclusion: Anomalies of the intracranial vasculature are common, and we describe a rare case of left MCA fenestration with an associated ruptured aneurysm at the site of the fenestration. In the literature, cases of fenestration of the MCA are sporadically reported and are only incidental findings.

Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells are destroyed in the islets of Langerhans. One of its main pathological manifestations is the hyper-expression of Major Histocompatibility Complex I (MHC-I) by beta cells, which was first described over 3 decades ago yet its cause remains unknown. It might not only be a sign of beta cell dysfunction but could also render the cells susceptible to autoimmune destruction; for example, by islet-infiltrating CD8 T cells. In this report, we studied pancreas tissue from a 22-year-old non-diabetic male cadaveric organ donor who had been at high risk of developing T1D, in which autoantibodies against GAD and IA-2 were detected. Pancreas sections were analyzed for signs of inflammation. Multiple insulin-containing islets were identified, which hyper-expressed MHC-I. However, islet density and MHC-I expression exhibited a highly lobular and heterogeneous pattern even within the same section. In addition, many islets with high expression of MHC-I presented higher levels of CD8 T cell infiltration than normal islets. These results demonstrate the heterogeneity of human pathology that occurs early during the pre-diabetic, autoantibody positive phase, and should contribute to the understanding of human T1D., (© The Author(s) 2015.)

Awareness of the renal vascular anatomy including variants of the renal vein is important for abdominal and renal surgeries, such as renal transplantation. The complex embryological development of the renal vein results in the following variations: additional renal veins on the left side, circum-aortic renal collar and retro-aortic renal veins. In this report, we present a case of a 35-year-old renal donor who had a rare renal vein anomaly that had been shown by computed tomography (CT) angiography. The left renal vein was single, and just before draining into the inferior vena cava (IVC) made two branches craniocaudally, which both passed posteriorly to the aorta and entered separately into the IVC.

Epicardial high-density electrical mapping is a well-established experimental instrument to monitor in vivo the activity of the atria in response to modulations of the autonomic nervous system in sinus rhythm. In regions that are not accessible by epicardial mapping, noncontact endocardial mapping performed through a balloon catheter may provide a more comprehensive description of atrial activity. We developed a computer model of the canine right atrium to compare epicardial and noncontact endocardial mapping. The model was derived from an experiment in which electroanatomical reconstruction, epicardial mapping (103 electrodes), noncontact endocardial mapping (2048 virtual electrodes computed from a 64-channel balloon catheter), and direct-contact endocardial catheter recordings were simultaneously performed in a dog. The recording system was simulated in the computer model. For simulations and experiments (after atrio-ventricular node suppression), activation maps were computed during sinus rhythm. Repolarization was assessed by measuring the area under the atrial T wave (ATa), a marker of repolarization gradients. Results showed an epicardial-endocardial correlation coefficients of 0.80 and 0.63 (two dog experiments) and 0.96 (simulation) between activation times, and a correlation coefficients of 0.57 and 0.46 (two dog experiments) and 0.92 (simulation) between ATa values. Despite distance (balloon-atrial wall) and dimension reduction (64 electrodes), some information about atrial repolarization remained present in noncontact signals.

Activation-induced cytidine deaminase (AID) introduces single-strand breaks (SSBs) to initiate class switch recombination (CSR), gene conversion (GC), and somatic hypermutation (SHM). CSR is mediated by double-strand breaks (DSBs) at donor and acceptor switch (S) regions, followed by pairing of DSB ends in two S regions and their joining. Because AID mutations at its C-terminal region drastically impair CSR but retain its DNA cleavage and SHM activity, the C-terminal region of AID likely is required for the recombination step after the DNA cleavage. To test this hypothesis, we analyzed the recombination junctions generated by AID C-terminal mutants and found that 0- to 3-bp microhomology junctions are relatively less abundant, possibly reflecting the defects of the classical nonhomologous end joining (C-NHEJ). Consistently, the accumulation of C-NHEJ factors such as Ku80 and XRCC4 was decreased at the cleaved S region. In contrast, an SSB-binding protein, poly (ADP)-ribose polymerase1, was recruited more abundantly, suggesting a defect in conversion from SSB to DSB. In addition, recruitment of critical DNA synapse factors such as 53BP1, DNA PKcs, and UNG at the S region was reduced during CSR. Furthermore, the chromosome conformation capture assay revealed that DNA synapse formation is impaired drastically in the AID C-terminal mutants. Interestingly, these mutants showed relative reduction in GC compared with SHM in chicken DT40 cells. Collectively, our data indicate that the C-terminal region of AID is required for efficient generation of DSB in CSR and GC and thus for the subsequent pairing of cleaved DNA ends during recombination in CSR.

Activation-induced cytidine deaminase (AID), which is both essential and sufficient for forming antibody memory, is also linked to tumorigenesis. AID is found in many B lymphomas, in myeloid leukemia, and in pathogen-induced tumors such as adult T cell leukemia. Although there is no solid evidence that AID causes human tumors, AID-transgenic and AID-deficient mouse models indicate that AID is both sufficient and required for tumorigenesis. Recently, AID's ability to cleave DNA has been shown to depend on topoisomerase 1 (Top1) and a histone H3K4 epigenetic mark. When the level of Top1 protein is decreased by AID activation, it induces irreversible cleavage in highly transcribed targets. This finding and others led to the idea that there is an evolutionary link between meiotic recombination and class switch recombination, which share H3K4 trimethyl, topoisomerase, the MRN complex, mismatch repair family proteins, and exonuclease 3. As Top1 has recently been shown to be involved in many transcription-associated genome instabilities, it is likely that AID took advantage of basic genome instability or diversification to evolve its mechanism for immune diversity. AID targets are therefore not highly specific to immunoglobulin genes and are relatively abundant, although they have strict requirements for transcription-induced H3K4 trimethyl modification and repetitive sequences prone to forming non-B structures. Inevitably, AID-dependent cleavage takes place in nonimmunoglobulin targets and eventually causes tumors. However, battles against infection are waged in the context of acute emergencies, while tumorigenesis is rather a chronic, long-term process. In the interest of survival, vertebrates must have evolved AID to prevent infection despite its long-term risk of causing tumorigenesis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Somatic hypermutation (SHM) and class-switch recombination (CSR) of the Ig gene require both the transcription of the locus and the expression of activation-induced cytidine deaminase (AID). During CSR, AID decreases the amount of topoisomerase I (Top1); this decrease alters the DNA structure and induces cleavage in the S region. Similarly, Top1 is involved in transcription-associated mutation at dinucleotide repeats in yeast and in triplet-repeat contraction in mammals. Here, we report that the AID-induced decrease in Top1 is critical for SHM. Top1 knockdown or haploinsufficiency enhanced SHM, whereas Top1 overexpression down-regulated it. A specific Top1 inhibitor, camptothecin, suppressed SHM, indicating that Top1's activity is required for DNA cleavage. Nonetheless, suppression of transcription abolished SHM, even in cells with Top1 knockdown, suggesting that transcription is critical. These results are consistent with a model proposed for CSR and triplet instability, in which transcription-induced non-B structure formation is enhanced by Top1 reduction and provides the target for irreversible cleavage by Top1. We speculate that the mechanism for transcription-coupled genome instability was adopted to generate immune diversity when AID evolved.

A single nucleotide polymorphism (SNP) in the adiponectin gene, 45T/G, has been reported in relation to a number of metabolic disorders, including obesity, insulin resistance, and diabetes. However, previous studies on the association between this SNP and the presence of coronary artery disease (CAD) have been few, with no report from Iranian subjects. The present study set out to investigate the association between this SNP and CAD in an Iranian population. Among 464 patients (age: 18-75 years), recruited from individuals who underwent coronary angiography, 135 patients had less than 50% reduction of coronary artery diameter and were classified as the CAD- group and 329 patients had more than 50% reduction of coronary artery diameter and were classified as the CAD+ group. The last group was divided into single-vessel disease (n = 86), two-vessel disease (n = 111), and three-vessel disease (n = 132). Healthy subjects (n = 106) who did not have any history of heart diseases were also recruited as the control group. All subjects were genotyped for the 45T/G polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. A significantly higher frequency of the TG genotype and G allele, which was paralleled by a lower frequency of the TT genotype and T allele, was observed in both CAD+ and CAD- patients when compared with the control group (p ≤ 0.001). There was no significant difference in the genotype distribution and allele frequencies between CAD+ and CAD- patients, and also between different subgroups of patients based on the number of stenosed vessels (p > 0.05). Our findings indicate that the presence of the G allele at the position +45 of the adiponectin gene may be associated with the risk of CAD in our study population. While we found no significant difference in the genotype distribution and allele frequencies between patients with angiography+ and angiography, this may be because the 50% stenosis cut-off does not discriminate sufficiently between individuals with and without significant coronary disease.

Background and Aims: The overall prevalence of obesity and metabolic syndrome (MetS) is increasing among children and adolescents and can predispose to type II diabetes mellitus and cardiovascular disease. There are reported associations between an angiotensin II type I receptor gene polymorphism (AT(1)R/A1166C) with hypertension, myocardial infarction, insulin resistance and cardiovascular disease risk. In the present study, we aimed to investigate whether the AT(1)R/A1166C polymorphism was associated with MetS among adolescent Iranian girls., Methods: A total of 350 adolescent girls aged 15-17 years from high schools and different educational zones of Mashhad city participated in this population-based, genetic association study. Of these individuals, 101 patients had MetS (defined by the NCEP-ATP III criteria); the remaining 249 age-matched girls were considered as the control group. All subjects were genotyped for the AT(1)R/A1166C polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique., Results: Frequencies of the AA, AC and CC genotypes were 164 (65.9%), 80 (32.1%) and 5 (2.0%) in the control group and 79 (78.2%), 20 (19.8%) and 2 (2.0%) in patients, which were not consistent with the Hardy-Weinberg equilibrium (p <0.05 and p <0.001, respectively). Frequency of the AT(1)R C allele was found to be significantly lower in patients compared with controls (p <0.05)., Conclusions: Our findings suggested that the 1166C allele of AT(1)R gene may be associated with a decreased risk of MetS in adolescent Iranian females., (Copyright © 2010 IMSS. Published by Elsevier Inc. All rights reserved.)