Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer.

The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.

A Multicenter Assessment of Interreader Reliability of LI-RADS Version 2018 for MRI and CT.

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

Aerophagia Study in Indonesia: Prevalence and Association With Family-related Stress.

BACKGROUND: Aerophagia is a functional gastrointestinal disorder characterized by repeated air swallowing leading to chronic abdominal distension. Symptoms can be long lasting, lead to frustration, and distress. This study describes prevalence, related factors, and symptomatology of aerophagia, together with its relationship with emotional stress. MATERIALS AND METHODS: Cross-sectional study. Adolescents aged 10 to 17 years from selected state schools by convenient sampling from Jakarta, Indonesia, were recruited. Rome III self-administered questionnaire was used to compile data on gastrointestinal symptoms. Data on sociodemographic characteristics, intestinal and extraintestinal symptoms, and stressful life events were collected using a separate questionnaire. RESULTS: A total of 1796 questionnaires were included in the analysis [males 732 (40.8%), mean age 13.58 (SD 0.992) years]. There were 81 (4.5%) subjects diagnosed with aerophagia. When the criterion of belching was removed from the diagnosis of aerophagia, the prevalence drops to only 2 (0.1%). subjects. Bivariate analysis showed that sociodemographic factors have no correlation with aerophagia. In subjects with aerophagia, among the intestinal-related and extraintestinal symptoms, only loss of appetite was significantly more common in the aerophagia population (33.3%) when compared with controls (22.8%). Death of a close family member [adjusted odds ratio (OR), 2.78; 95% confidence interval (CI), 1.46-5.31; P=0.002], divorce or separation of parents (adjusted OR, 2.54; 95% CI, 1.38-4.66; P=0.003), and divorce followed by separate individual remarriage of parents (adjusted OR, 2.01; 95% CI, 1.01-3.98; P=0.046) were found to be significantly associated with aerophagia by multivariate analysis. CONCLUSIONS: The prevalence of aerophagia was found in 4.5% of Indonesian school-aged children according to Rome III criteria, but the prevalence was found only 0.1% if the belching is removed from the criteria. Besides the main symptoms, only loss of appetite was significantly more common in aerophagia among intestinal-related and extraintestinal symptoms. Family-related stress showed a significant correlation with aerophagia.

The pig X and Y Chromosomes: structure, sequence, and evolution.

We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which are protein coding. Gene order closely matches that found in primates (including humans) and carnivores (including cats and dogs), which is inferred to be ancestral. Nevertheless, several protein-coding genes present on the human X Chromosome were absent from the pig, and 38 pig-specific X-chromosomal genes were annotated, 22 of which were olfactory receptors. The pig Y-specific Chromosome sequence generated here comprises 30 megabases (Mb). A 15-Mb subset of this sequence was assembled, revealing two clusters of male-specific low copy number genes, separated by an ampliconic region including the HSFY gene family, which together make up most of the short arm. Both clusters contain palindromes with high sequence identity, presumably maintained by gene conversion. Many of the ancestral X-related genes previously reported in at least one mammalian Y Chromosome are represented either as active genes or partial sequences. This sequencing project has allowed us to identify genes--both single copy and amplified--on the pig Y Chromosome, to compare the pig X and Y Chromosomes for homologous sequences, and thereby to reveal mechanisms underlying pig X and Y Chromosome evolution.

Supplementation With Lactoferrin and Lysozyme Ameliorates Environmental Enteric Dysfunction: A Double-Blind, Randomized, Placebo-Controlled Trial.

INTRODUCTION: Environmental enteric dysfunction (EED) predisposes children throughout the developing world to high rates of systemic exposure to enteric pathogens and stunting. Effective interventions that treat or prevent EED may help children achieve their full physical and cognitive potential. The objective of this study is to test whether 2 components of breast milk would improve a biomarker of EED and linear growth during the second year of life. METHODS: A prospective, randomized, double-blind, placebo-controlled clinical trial among children aged 12-23 months was conducted in rural Malawi. The experimental group received a daily supplement of 1.5 g of lactoferrin and 0.2 g of lysozyme for 16 weeks. The primary outcome was an improvement in EED, as measured by the change in the percentage of ingested lactulose excreted into the urine (Δ%L). RESULTS: Among 214 children who completed the study, there was a significant difference in Δ%L between the control and experimental groups over 8 weeks (an increase of 0.23% vs 0.14%, respectively; P = 0.04). However, this relative improvement was not as strongly sustained over the full 16 weeks of the study (an increase of 0.16% vs 0.11%, respectively; P = 0.17). No difference in linear growth over this short period was observed. The experimental intervention group had significantly lower rates of hospitalization and the development of acute malnutrition during the course of the study (2.5% vs 10.3%, relative risk 0.25; P < 0.02). DISCUSSION: Supplementation with lactoferrin and lysozyme in a population of agrarian children during the second year of life has a beneficial effect on gut health. This intervention also protected against hospitalization and the development of acute malnutrition, a finding with a significant clinical and public health importance. This finding should be pursued in larger studies with longer follow-up and optimized dosing.

Longitudinal evolution of CT and MRI LI-RADS v2014 category 1, 2, 3, and 4 observations.

OBJECTIVES: This study assesses the risk of progression of Liver Imaging Reporting and Data System (LI-RADS) categories, and the effects of inter-exam changes in modality or radiologist on LI-RADS categorization. METHODS: Clinical LI-RADS v2014 CT and MRI exams at our institution between January 2014 and September 2017 were retrospectively identified. Untreated LR-1, LR-2, LR-3, and LR-4 observations with at least one follow-up exam were included. Three hundred and seventy-two observations in 214 patients (149 male, 65 female, mean age 61 ± 10 years) were included during the study period (715 exams total). Cumulative incidence curves for progression to malignant LI-RADS categories (LR-5 or LR-M) and to LR-4 or higher were generated for each index category and compared using log-rank tests with a resampling extension. Relationships between inter-exam changes in LI-RADS category and modality or radiologist, adjusted for inter-exam time intervals, were modeled using mixed effect logistic regressions. RESULTS: Median inter-exam follow-up interval and total follow-up duration were 123 and 227 days, respectively. Index LR-1, LR-2, LR-3, and LR-4 differed significantly in their cumulative incidences of progression to malignant categories (p < 0.0001), which were 0%, 2%, 7%, and 32% at 6 months, respectively. Index LR-1, LR-2, and LR-3 differed significantly in cumulative incidences of progression to LR-4 or higher (p = 0.003). MRI-MRI exam pairs had more stable LI-RADS categorization compared to CT-CT (OR = 0.460, p = 0.0018). CONCLUSIONS: LI-RADS observations demonstrate increasing risk of progression to malignancy with increasing category ranging from 0% for LR-1 to 32% for LR-4 at 6 months. Inter-exam modality changes are associated with LI-RADS category changes. KEY POINTS: • While the majority of LR-2 observations remain stable over long-term follow-up, LR-3 and especially LR-4 observations have a higher risk for category progression. • Category transitions between sequential exams using different modalities (CT vs. MRI) may reflect modality differences rather than biological change. MRI, especially with the same type of contrast agent, may provide the most reproducible categorization, although this needs additional validation. • In a clinical practice setting, in which radiologists refer to prior imaging and reports, there was no significant association between changes in radiologist and changes in LI-RADS categorization.

Hepatic steatosis and reduction in steatosis following bariatric weight loss surgery differs between segments and lobes.

OBJECTIVES: The purpose of this study was to (1) evaluate proton density fat fraction (PDFF) distribution across liver segments at baseline and (2) compare longitudinal segmental PDFF changes across time points in adult patients undergoing a very low-calorie diet (VLCD) and subsequent bariatric weight loss surgery (WLS). METHODS: We performed a secondary analysis of data from 118 morbidly obese adult patients enrolled in a VLCD-WLS program. PDFF was estimated using magnitude-based confounder-corrected chemical-shift-encoded (CSE) MRI in each hepatic segment and lobe at baseline (visit 1), after completion of VLCD (visit 2), and at 1, 3, and 6 months (visits 3-5) following WLS. Linear regressions were used to estimate the rate of PDFF change across visits. Lobar and segmental rates of change were compared pairwise. RESULTS: Baseline PDFF was significantly higher in the right lobe compared to the left lobe (p < 0.0001). Lobar and segmental PDFF declined by 3.9-4.5% per month between visits 1 and 2 (preoperative period) and by 4.3-4.8% per month between visits 1 and 3 (perioperative period), but no significant pairwise differences were found in slope between segments and lobes. For visits 3-5 (postoperative period), lobar and segmental PDFF reduction was much less overall (0.4-0.8% PDFF per month) and several pairwise differences were significant; in each case, a right-lobe segment had greater decline than a left-lobe segment. CONCLUSIONS: Baseline and longitudinal changes in fractional fat content in the 5-month postoperative period following WLS vary across segments, with right-lobe segments having higher PDFF at baseline and more rapid reduction in liver fat content. KEY POINTS: • Baseline and longitudinal changes in liver fat following bariatric weight loss surgery vary across liver segments. • Methods that do not provide whole liver fat assessment, such as liver biopsy, may be unreliable in monitoring longitudinal changes in liver fat following weight loss interventions.

Functional abdominal pain disorders in adolescents in Indonesia and their association with family related stress.

BACKGROUND: Functional abdominal pain disorders (FAPD) have been widely reported as a major group of gastrointestinal disorders across the world. This study describes the prevalence, related factors, symptomatology and its relationship to emotional stress in Indonesian adolescents. METHODS: This is a cross-sectional study. Adolescents aged 10 to 17 years from nine randomly selected state schools from five districts of Jakarta, Indonesia, were invited to participate. A translated and validated Rome-III self-administered-questionnaire was used to collect data on gastrointestinal symptoms. Data on sociodemographic characteristics, intestinal as well as extra-intestinal symptoms, and exposure to stressful life events were also collected using a separate validated questionnaire. RESULTS: A total of 1813 questionnaires were included in the analysis [males 739 (40.8%) mean age of 13.54 years + 0.89]. Of them, 209 children (11.5%) fulfilled Rome III criteria of FAPD. Functional abdominal pain (FAP) was reported as the most prevalent subtype (5.8%), followed by functional dyspepsia (3.3%), irritable bowel syndrome (2%) and abdominal migraine (0.4%). The prevalence was higher in girls (p < 0.05) and those exposed to family-related stressful life events (p < 0.05). They include divorce or separation of parents (adjusted OR 2.55, 95% CI 1.75-3.7, p = < 0.001), death of a close family member (adjusted OR 2.24, 95% CI 1.39-3.59, P = 0.001), and father's alcoholism (adjusted OR 1.94, 95% CI 1.22-3.1, P = 0.005). CONCLUSIONS: FAPD are common paediatric entities among Indonesian adolescents with a prevalence of 11.5%. FAPD were noted to be higher in girls and adolescents exposed to family-related stressful life events.

Quantitative Elastography Methods in Liver Disease: Current Evidence and Future Directions.

Chronic liver diseases often result in the development of liver fibrosis and ultimately, cirrhosis. Treatment strategies and prognosis differ greatly depending on the severity of liver fibrosis, thus liver fibrosis staging is clinically relevant. Traditionally, liver biopsy has been the method of choice for fibrosis evaluation. Because of liver biopsy limitations, noninvasive methods have become a key research interest in the field. Elastography enables the noninvasive measurement of tissue mechanical properties through observation of shear-wave propagation in the tissue of interest. Increasing fibrosis stage is associated with increased liver stiffness, providing a discriminatory feature that can be exploited by elastographic methods. Ultrasonographic (US) and magnetic resonance (MR) imaging elastographic methods are commercially available, each with their respective strengths and limitations. Here, the authors review the technical basis, acquisition techniques, and results and limitations of US- and MR-based elastography techniques. Diagnostic performance in the most common etiologies of chronic liver disease will be presented. Reliability, reproducibility, failure rate, and emerging advances will be discussed. © RSNA, 2018 Online supplemental material is available for this article.

MRI proton density fat fraction is robust across the biologically plausible range of triglyceride spectra in adults with nonalcoholic steatohepatitis.

BACKGROUND: Proton density fat fraction (PDFF) estimation requires spectral modeling of the hepatic triglyceride (TG) signal. Deviations in the TG spectrum may occur, leading to bias in PDFF quantification. PURPOSE: To investigate the effects of varying six-peak TG spectral models on PDFF estimation bias. STUDY TYPE: Retrospective secondary analysis of prospectively acquired clinical research data. POPULATION: Forty-four adults with biopsy-confirmed nonalcoholic steatohepatitis. FIELD STRENGTH/SEQUENCE: Confounder-corrected chemical-shift-encoded 3T MRI (using a 2D multiecho gradient-recalled echo technique with magnitude reconstruction) and MR spectroscopy. ASSESSMENT: In each patient, 61 pairs of colocalized MRI-PDFF and MRS-PDFF values were estimated: one pair used the standard six-peak spectral model, the other 60 were six-peak variants calculated by adjusting spectral model parameters over their biologically plausible ranges. MRI-PDFF values calculated using each variant model and the standard model were compared, and the agreement between MRI-PDFF and MRS-PDFF was assessed. STATISTICAL TESTS: MRS-PDFF and MRI-PDFF were summarized descriptively. Bland-Altman (BA) analyses were performed between PDFF values calculated using each variant model and the standard model. Linear regressions were performed between BA biases and mean PDFF values for each variant model, and between MRI-PDFF and MRS-PDFF. RESULTS: Using the standard model, mean MRS-PDFF of the study population was 17.9 ± 8.0% (range: 4.1-34.3%). The difference between the highest and lowest mean variant MRI-PDFF values was 1.5%. Relative to the standard model, the model with the greatest absolute BA bias overestimated PDFF by 1.2%. Bias increased with increasing PDFF (P < 0.0001 for 59 of the 60 variant models). MRI-PDFF and MRS-PDFF agreed closely for all variant models (R2 = 0.980, P < 0.0001). DATA CONCLUSION: Over a wide range of hepatic fat content, PDFF estimation is robust across the biologically plausible range of TG spectra. Although absolute estimation bias increased with higher PDFF, its magnitude was small and unlikely to be clinically meaningful. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:995-1002.

Optimization of region-of-interest sampling strategies for hepatic MRI proton density fat fraction quantification.

BACKGROUND: Clinical trials utilizing proton density fat fraction (PDFF) as an imaging biomarker for hepatic steatosis have used a laborious region-of-interest (ROI) sampling strategy of placing an ROI in each hepatic segment. PURPOSE: To identify a strategy with the fewest ROIs that consistently achieves close agreement with the nine-ROI strategy. STUDY TYPE: Retrospective secondary analysis of prospectively acquired clinical research data. POPULATION: A total of 391 adults (173 men, 218 women) with known or suspected NAFLD. FIELD STRENGTH/SEQUENCE: Confounder-corrected chemical-shift-encoded 3T MRI using a 2D multiecho gradient-recalled echo technique. ASSESSMENT: An ROI was placed in each hepatic segment. Mean nine-ROI PDFF and segmental PDFF standard deviation were computed. Segmental and lobar PDFF were compared. PDFF was estimated using every combinatorial subset of ROIs and compared to the nine-ROI average. STATISTICAL TESTING: Mean nine-ROI PDFF and segmental PDFF standard deviation were summarized descriptively. Segmental PDFF was compared using a one-way analysis of variance, and lobar PDFF was compared using a paired t-test and a Bland-Altman analysis. The PDFF estimated by every subset of ROIs was informally compared to the nine-ROI average using median intraclass correlation coefficients (ICCs) and Bland-Altman analyses. RESULTS: The study population's mean whole-liver PDFF was 10.1 ± 8.9% (range: 1.1-44.1%). Although there was no significant difference in average segmental (P = 0.452) or lobar (P = 0.154) PDFF, left and right lobe PDFF differed by at least 1.5 percentage points in 25.1% (98/391) of patients. Any strategy with ≥4 ROIs had ICC >0.995. 115 of 126 four-ROI strategies (91%) had limits of agreement (LOA) <1.5%, including four-ROI strategies with two ROIs from each lobe, which all had LOA <1.5%. 14/36 (39%) of two-ROI strategies and 74/84 (88%) of three-ROI strategies had ICC >0.995, and 2/36 (6%) of two-ROI strategies and 46/84 (55%) of three-ROI strategies had LOA <1.5%. DATA CONCLUSION: Four-ROI sampling strategies with two ROIs in the left and right lobes achieve close agreement with nine-ROI PDFF. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:988-994.

Cross-sectional correlation between hepatic R2* and proton density fat fraction (PDFF) in children with hepatic steatosis.

PURPOSE: To determine the relationship between hepatic proton density fat fraction (PDFF) and R2* in vivo. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act (HIPAA)-compliant, Institutional Review Board (IRB)-approved, cross-sectional study, we conducted a secondary analysis of 3T magnetic resonance imaging (MRI) exams performed as part of prospective research studies in children in whom conditions associated with iron overload were excluded clinically. Each exam included low-flip-angle, multiecho magnitude (-M) and complex (-C) based chemical-shift-encoded MRI techniques with spectral modeling of fat to generate hepatic PDFF and R2* parametric maps. For each technique and each patient, regions of interest were placed on the maps in each of the nine Couinaud segments, and composite whole-liver PDFF and R2* values were calculated. Pearson's correlation coefficients between PDFF and R2* were computed for each MRI technique. Correlations were compared using Steiger's test. RESULTS: In all, 184 children (123 boys, 61 girls) were included in this analysis. PDFF estimated by MRI-M and MRI-C ranged from 1.1-35.4% (9.44 ± 8.76) and 2.1-38.1% (10.1 ± 8.7), respectively. R2* estimated by MRI-M and MRI-C ranged from 32.6-78.7 s-1 (48.4 ± 9.8) and 27.2-71.5 s-1 (42.2 ± 8.6), respectively. There were strong and significant correlations between hepatic PDFF and R2* values estimated by MRI-M (r = 0.874; P < 0.0001) and MRI-C (r = 0.853; P < 0.0001). The correlation coefficients (0.874 vs. 0.853) were not significantly different (P = 0.15). CONCLUSION: Hepatic PDFF and R2* are strongly correlated with each other in vivo. This relationship was observed using two different MRI techniques. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:418-424.

Epidemiology of Paediatric constipation in Indonesia and its association with exposure to stressful life events.

BACKGROUND: We aimed to study the epidemiology and risk factors, including exposure to emotional stress, for constipation in Indonesian children and adolescents of 10-17 year age group. METHODS: A cross-sectional survey using a validated, self-administered questionnaire was conducted in randomly selected children and adolescents in nine state junior high schools from five districts of Jakarta. All of them were from urban areas. Constipation was defined as a diagnosis by using the Rome III criteria. RESULTS: Of 1796 children included in the analysis, 328 (18.3%; 95% CI 016-0.2) had constipation. Females and those residing in North Jakarta showed risks associated with constipation in school-age children and adolescents. Symptoms independently associated with constipation were abdominal pain (64% vs 43.3% of control) and straining (22.9% vs 6.3%). The prevalence of constipation was significantly higher in those with stressful life events such as father's alcoholism (adjusted OR 1.91, 95% CI 1.27-2.89, P = 0.002), severe illness of a close family member (adjusted OR 1.77, 95% CI 1.12-2.80, P = 0.014), hospitalization of the child for another illness (adjusted OR 1.68, 95% CI 1.22-2.31, P < 0.001), being bullied at school (adjusted OR 1.67, 95% CI 1.01-2.76, P = 0.047) and loss of a parent's job (adjusted OR 1.39, 95% CI 1.03-1.88, P = 0.034). CONCLUSIONS: Constipation in children and adolescent is a significant health problem, affecting almost 20% of Indonesian school-age children and adolescents. Common school and home related stressful life events appear to have predisposed these children to develop constipation.

Chronic recurrent multifocal osteomyelitis with an atypical presentation in an adult man.

We present the case of a 33-year-old man with no significant medical history who developed right scapular pain, left-sided sacroiliac joint pain, and lower back pain, and was eventually diagnosed with chronic recurrent multifocal osteomyelitis (CRMO). Imaging demonstrated multiple scattered T2-hyperintense lesions on MRI at the spine and the left SI joint, some of which progressed and one regressed in size on follow-up. Histopathology demonstrated only non-specific chronic inflammation compatible with CRMO. No evidence of infectious organisms or neoplastic processes was found. The pain was relapsing and remitting in nature. Laboratory investigations were notable for no evidence of hematologic malignancy or infection, but only a mild increase in alkaline phosphatase. This case highlights that CRMO, despite being thought of as a childhood-onset disease, can present in adults as well, and also provides illustrative examples of imaging and histological findings.

Prostate biopsy for the interventional radiologist.

Prostate biopsies are usually performed by urologists in the office setting using transrectal ultrasound (US) guidance. The current standard of care involves obtaining 10-14 cores from different anatomic sections. Biopsies are usually not directed into a specific lesion because most prostate cancers are not visible on transrectal US. Color Doppler, US contrast agents, elastography, magnetic resonance (MR) imaging, and MR imaging/US fusion are proposed as imaging methods to guide prostate biopsies. Prostate MR imaging and fusion biopsy create opportunities for diagnostic and interventional radiologists to play an increasingly important role in the screening, evaluation, diagnosis, targeted biopsy, surveillance, and focal therapy of patients with prostate cancer.

Chromosomal evolution among leaf-nosed nectarivorous bats--evidence from cross-species chromosome painting (Phyllostomidae, Chiroptera).

BACKGROUND: New World leaf-nosed bats, Phyllostomidae, represent a lineage of Chiroptera marked by unprecedented morphological/ecological diversity and extensive intergeneric chromosomal reorganization. There are still disagreements regarding their systematic relationships due to morphological convergence among some groups. Their history of karyotypic evolution also remains to be documented. RESULTS: To better understand the evolutionary relationships within Phyllostomidae, we developed chromosome paints from the bat species Macrotus californicus. We tested the potential of these paints as phylogenetic tools by looking for chromosomal signatures in two lineages of nectarivorous phyllostomids whose independent origins have been statistically supported by molecular phylogenies. By examining the chromosomal homologies defined by chromosome painting among two representatives of the subfamily Glossophaginae (Glossophaga soricina and Anoura cultrata) and one species from the subfamily Lonchophyllinae (Lonchophylla concava), we found chromosomal correspondence in regions not previously detected by other comparative cytogenetic techniques. We proposed the corresponding human chromosomal segments for chromosomes of the investigated species and found two syntenic associations shared by G. soricina and A. cultrata. CONCLUSION: Comparative painting with whole chromosome-specific paints of M. californicus demonstrates an extensive chromosomal reorganization within the two lineages of nectarivorous phyllostomids, with a large number of chromosomes shared between M. californicus and G. soricina. We show that the evolution of nectar-feeding bats occurs mainly by reshuffling of chiropteran Evolutionarily Conserved Units (ECUs). Robertsonian fusions/fissions and inversions seem to be important modifiers of phyllostomid karyotypes, and autapomorphic character states are common within species. Macrotus californicus chromosome paints will be a valuable tool for documenting the pattern of karyotypic evolution within Phyllostomidae radiation.

Common genetic variants regulating ADD3 gene expression alter biliary atresia risk.

BACKGROUND & AIMS: Biliary atresia (BA) is a rare and most severe cholestatic disease in neonates, but the pathogenic mechanisms are unknown. Through a previous genome wide association study (GWAS) on Han Chinese, we discovered association of the 10q24.2 region encompassing ADD3 and XPNPEP1 genes, which was replicated in Chinese and Thai populations. This study aims to fully characterize the genetic architecture at 10q24.2 and to reveal the link between the genetic variants and BA. METHODS: We genotyped 107 single nucleotide polymorphisms (SNPs) in 10q24.2 in 339 Han Chinese patients and 401 matched controls using Sequenom. Exhaustive follow-up studies of the association signals were performed. RESULTS: The combined BA-association p-value of the GWAS SNP (rs17095355) achieved 6.06×10(-10). Further, we revealed the common risk haplotype encompassing 5 tagging-SNPs, capturing the risk-predisposing alleles in 10q24.2 [p=5.32×10(-11); odds ratio, OR: 2.38; confidence interval, CI: (2.14-2.62)]. Through Sanger sequencing, no deleterious rare variants (RVs) residing in the risk haplotype were found, dismissing the theory of "synthetic" association. Moreover, in bioinformatics and in vivo genotype-expression investigations, the BA-associated potentially regulatory SNPs correlated with ADD3 gene expression (n=36; p=0.0030). Remarkably, the risk haplotype frequency coincides with BA incidences in the population, and, positive selection (favoring the derived alleles that arose from mutations) was evident at the ADD3 locus, suggesting a possible role for the BA-associated common variants in shaping the general population diversity. CONCLUSIONS: Common genetic variants in 10q24.2 can alter BA risk by regulating ADD3 expression levels in the liver, and may exert an effect on disease epidemiology and on the general population.

Can magnetic resonance-ultrasound fusion biopsy improve cancer detection in enlarged prostates?

PURPOSE: Patients with an enlarged prostate and suspicion of prostate cancer pose a diagnostic dilemma. The prostate cancer detection rate of systematic 12-core transrectal ultrasound guided biopsy is between 30% and 40%. For prostates greater than 40 cc this decreases to 30% or less. Magnetic resonance-ultrasound fusion biopsy has shown superior prostate cancer detection rates. We defined the detection rate of magnetic resonance-ultrasound fusion biopsy in men with an enlarged prostate gland. MATERIALS AND METHODS: We retrospectively analyzed the records of patients who underwent multiparametric prostate magnetic resonance imaging followed by magnetic resonance-ultrasound fusion biopsy at our institution. Whole prostate volumes were calculated using magnetic resonance imaging reconstructions. Detection rates were analyzed with respect to age, prostate specific antigen and whole prostate volumes. Multivariable logistic regression was used to assess these parameters as independent predictors of prostate cancer detection. RESULTS: We analyzed 649 patients with a mean±SD age of 61.8±7.9 years and a median prostate specific antigen of 6.65 ng/ml (IQR 4.35-11.0). Mean whole prostate volume was 58.7±34.3 cc. The overall detection rate of the magnetic resonance-ultrasound fusion platform was 55%. For prostates less than 40 cc the detection rate was 71.1% compared to 57.5%, 46.9%, 46.9% 33.3%, 36.4% and 30.4% for glands 40 to 54.9, 55 to 69.9, 70 to 84.9, 85 to 99.9, 100 to 114.9 and 115 cc or greater, respectively (p<0.0001). Multivariable logistic regression showed a significant inverse association of magnetic resonance imaging volume with prostate cancer detection, controlling for age and prostate specific antigen. CONCLUSIONS: Transrectal ultrasound guided and fusion biopsy cancer detection rates decreased with increasing prostate volume. However, magnetic resonance-ultrasound fusion biopsy had a higher prostate cancer detection rate compared to that of transrectal ultrasound guided biopsy in the literature. Magnetic resonance-ultrasound fusion biopsy represents a promising solution for patients with suspicion of prostate cancer and an enlarged prostate.

Impact of non-cardiovascular surgery on reactive hyperaemia and arterial endothelial function.

Vascular reactivity is a surrogate marker for atherosclerosis and is predictive of cardiovascular outcome. Non-cardiovascular surgery is associated with perioperative cardiovascular complications in high-risk patients. To evaluate the impact of non-cardiovascular surgery on reactive hyperaemia and arterial endothelial function and to investigate the relationships between endothelial dysfunction and invasive (laparotomy) or minimally invasive (laparoscopic) surgery, we prospectively evaluated 106 patients undergoing abdominal surgery under general anaesthesia (71 laparotomy, 35 laparoscopy). Measurements of blood pressure, heart rate and pain (on a visual analogue scale (VAS)) were undertaken. Brachial endothelium-dependent flow-mediated dilation (FMD), endothelium-independent dilation, nitroglycerin (NTG)-induced dilation and reactive hyperaemia were measured with high-resolution B-mode ultrasound on preoperative Day 1 (baseline), as well as 2 h and 1 and 7 days postoperatively. Blood pressure and heart rate were significantly higher 2 h postoperatively. Pain, as measured on the VAS, was higher (P < 0.01) and reactive hyperaemia and FMD were significantly lower (P < 0.001) at 2 h and 1 day postoperatively compared with values at baseline and on postoperative Day 7. By postoperative Day 7, FMD had recovered to baseline levels. Patients undergoing laparoscopic surgery had less FMD reduction on Days 1 and 7 (7.5 ± 1.5% and 7.9 ± 1.5%, respectively) compared with those undergoing laparotomy (6.4 ± 1.6% (P = 0.001) and 7.0 ± 1.6% (P = 0.006), respectively), consistent with potential cardiovascular benefit. Responses to NTG were stable throughout. Backward multivariate linear regression analysis indicated that FMD was independently related to age and VAS (model R = 0.486; F = 6.4; P < 0.001). Reactive hyperaemia and arterial endothelial function are significantly reduced in the early postoperative period, particularly after laparotomy compared with laparoscopy, which may be related to postoperative cardiovascular events.