F0 F1 Research Articles

Asymmetrical positive assortative mating induced by developmental lead (Pb2+) exposure in a model system, Drosophila melanogaster.

Anthropogenic pollutants have the potential to disrupt reproductive strategies. Little is known about how lead (Pb2+) exposure disrupts individual-level responses in reproductive behaviors, which are important for fitness. Drosophila melanogaster was used as a model system to determine the effects of: 1) developmental lead exposure on pre-mating reproductive behaviors (i.e., mate preference), and 2) lead exposure and mating preferences on fitness in the F0 parental generation and F1 un-exposed offspring. Wild-type strains of D. melanogaster were reared from egg stage to adulthood in control or leaded medium (250 μM PbAc) and tested for differences in: mate preference, male song performance, sex pheromone expression, fecundity, mortality, and body weight. F0 leaded females preferentially mated with leaded males (i.e., asymmetrical positive assortative mating) in 2-choice tests. This positive assortative mating was mediated by the females (and not the males) and was dependent upon context and developmental exposure to Pb. Neither the courtship song nor the sex pheromone profile expressed by control and leaded males mediated the positive assortative mating in leaded females. Leaded females did not incur a fitness cost in terms of reduced fecundity, increased mortality, or decreased body weight by mating with leaded males. These results suggest that sublethal exposure to lead during development can alter mate preferences in adults, but not fitness measures once lead exposure has been removed. We suggest that changes in mate preference may induce fitness costs, as well as long-term population and multi-generational implications, if pollution is persistent in the environment.

Вміст мікроелементів у тканинах самиць щурів F0 та самців F1 за випоювання нано і хімічно синтезованого германію цитрату

Вміст мікроелементів у тканинах самиць щурів F0 та самців F1 за випоювання нано і хімічно синтезованого германію цитрату

Liver fibrosis regression and progression during controlled hepatitis B virus infection among HIV-HBV patients treated with tenofovir disoproxil fumarate in France: a prospective cohort study.

Introduction: Long-term tenofovir disoproxil fumarate (TDF) use has been associated with significant regression of liver fibrosis during hepatitis B virus (HBV) mono-infection, yet little is known during HIV–HBV coinfection. The aim of this study was to evaluate the evolution of liver fibrosis and its determinants in TDF-treated coinfected patients. Methods: In this prospective cohort study, 167 HIV–HBV-infected patients initiating TDF-containing antiretroviral therapy were included. Fibrosis was assessed using the FibroTest® at baseline and every six to twelve months. Risk factors for fibrosis progression (F0–F1–F2 to F3–F4) and regression (F3–F4 to F0–F1–F2) were evaluated. Results: At baseline, 134 (80.2%) patients had detectable HBV-DNA (median = 4.93 log10 IU/mL, IQR = 2.94–7.15) and 104 (62.3%) had hepatitis B “e” antigen-positive serology. Median follow-up was sixty months (IQR = 36–93). In the 47 (28.1%) patients with F3–F4 baseline fibrosis, 7/47 (14.9%) regressed to F0–F1–F2 at last follow-up visit. Fibrosis regression was significantly associated with higher CD4+ cell counts (P = 0.009) and lower fasting triglyceride levels (P = 0.007) at TDF-initiation. In the 120 (71.9%) patients with F0–F1–F2-baseline fibrosis, 20/120 (16.7%) progressed to F3–F4 at last follow-up visit. Fibrosis progression was associated with male gender (P = 0.01), older age (P = 0.001), from low/moderate HBV-endemic country (P = 0.007), lower nadir CD4+ cell count (P = 0.03), higher fasting glycaemia (P = 0.03) and anaemia (P = 0.004) at TDF-initiation. Control of HBV replication at end of follow-up was extensive (88.1%), while no HBV-related factors emerged as predictors of progression/regression. Incidence of severe liver-related events was low (n = 4, rate = 0.5/100 person-years). Conclusions: Liver fibrosis levels are stable for most coinfected patients undergoing TDF, despite control of HBV replication. Nevertheless, a concerning amount of liver fibrosis progression did occur, which could be partly explained by metabolic abnormalities and past severe immunosuppression and requires further evaluation.

Developmental bisphenol A exposure impairs sperm function and reproduction in zebrafish

The developmental and reproductive toxicity of bisphenol A (BPA) has been demonstrated in a variety of model systems. Zebrafish (Danio rerio) were waterborne-exposed to BPA during three different developmental stages: embryonic period:6 h post fertilization (hpf) to 5 months post fertilization (mpf); larval period: 6 days post fertilization (dpf) to 5 mpf; and sexually mature period: 3 mpf to 5 mpf. Evaluations included F0 adult growth, reproduction parameters, and F1 offspring development. BPA exposure did not affect zebrafish growth in any of exposure groups. Testis weight was decreased only following the 6 hpf to 5 mpf 0.001 μM BPA exposure. The lowest effect level indicated by a reduction in sperm volume, density, motility, and velocity across a range of exposure durations was 0.001 μM, with all but sperm density significant for the longest exposure duration, which was also the only significant endpoint for the lowest exposure concentration in the 3–5 mpf exposure group. Nonmonotonic concentration-response curves were noted for all F0 reproductive endpoints for at least one of the two longest exposure durations. For the F1 offspring of fish exposed from 6 hpf to 5 mpf, malformations and mortality were increased following 0.001 μM BPA exposure, while egg production and fertilization were reduced in higher concentration treatment groups. Overall, BPA exposure during three different developmental periods impaired zebrafish reproductive development, with most significance changes found in the lowest concentration treatment groups. Genetic impacts on gamete development may underlie the secondary effects of reduced fertilization rate, embryonic mortality, and malformations.

Model-dependent and model-independent approaches for evaluating hepatic fibrosis in rat liver using shearwave dispersion ultrasound vibrometry

This study assesses gradations of hepatic fibrosis in rat livers using both model-dependent and model-independent approaches. Liver fibrosis was induced in 37 rats using carbon tetrachloride (CCl4); 6 rats served as the controls. Shear wave velocity as a function of frequency, referred to as velocity dispersion, was measured in vitro by an ultrasound elastography method called shearwave dispersion ultrasound vibrometry (SDUV). For the model-dependent approach, the velocity dispersion data were fit to the Voigt model to solve the viscoelastic modulus. For the model-independent approach, the pattern of the velocity dispersion data was analyzed by linear regression to extract the slope and intercept features. The parameters obtained by both approaches were evaluated separately using a receiver operating characteristic (ROC) curve analysis. The results show that, of all the parameters for differentiating between grade F0–F1 and grade F2–F4 fibrosis, the intercept had the greatest value for the area under the ROC curve. This finding suggests that the model-independent approach may provide an alternative method to the model-dependent approach for staging liver fibrosis.

Transient elastography as a noninvasive assessment tool for hepatopathies of different etiology in pediatric type 1 diabetes mellitus

AimTo identify the prevalence and effect of hepatopathies of different etiologies among pediatric patients with type 1 diabetes mellitus (T1DM) using transient elastography (TE) and its relation to glycemic control. MethodsOne hundred T1DM patients were studied focusing on liver functions, fasting lipid profile, hemoglobin A1c (HbA1c), hepatitis C virus (HCV), serum immunoglobulins, autoimmune antibodies; anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-liver kidney microsomal antibody (anti-LKM). Abdominal ultrasound was performed and TE was done for patients with HCV, positive autoimmune antibody and/or abnormal ultrasound findings. ResultsThirty-one patients were found to have one or more hepatic abnormalities; clinical hepatomegaly in 8%, elevated alanine aminotransferase (ALT) in 10%, HCV in 6%, autoimmune hepatitis (AIH) in 11% (10 were positive for ASMA and 2 were positive for ANA while anti-LKM antibodies were negative) and abnormal hepatic ultrasound in 20% (12 non-alcoholic fatty liver disease, 5 AIH, 2 HCV, 1 Mauriac syndrome). Mean liver stiffness in those 31 patients was 7.0±2.1kPa (range, 3.1–11.8kPa); 24 were Metavir F0–F1, 7 were F2–F3 while none was F4. Type 1 diabetic patients with abnormal hepatic ultrasound had higher fasting blood glucose, HbA1c and total cholesterol than those with normal findings. Liver stiffness was significantly higher in patients with abnormal liver ultrasound compared with normal sonography. Liver stiffness was positively correlated to HbA1c and ALT. ConclusionsHepatic abnormalities are prevalent in T1DM and related to poor metabolic control. TE provides a non-invasive method for detection of hepatopathy-induced fibrosis.

The genetic basis of discrete and quantitative colour variation in the polymorphic lizard, Ctenophorus decresii.

BackgroundColour polymorphic species provide invaluable insight into processes that generate and maintain intra-specific variation. Despite an increasing understanding of the genetic basis of discrete morphs, sources of colour variation within morphs remain poorly understood. Here we use the polymorphic tawny dragon lizard Ctenophorus decresii to test simple Mendelian models for the inheritance of discrete morphs, and to investigate the genetic basis of continuous variation among individuals across morphs. Males of this species express either orange, yellow, orange surrounded by yellow, or grey throats. Although four discrete morphs are recognised, the extent of orange and yellow varies greatly. We artificially elevated testosterone in F0 females and F1 juveniles to induce them to express the male throat colour polymorphism, and quantified colour variation across the pedigree.ResultsInheritance of discrete morphs in C. decresii best fit a model whereby two autosomal loci with complete dominance respectively determine the presence of orange and yellow. However, a single locus model with three co-dominant alleles for orange, yellow and grey could not be definitively rejected. Additionally, quantitative expression of the proportion of orange and yellow on the throat was strongly heritable (orange: h2 = 0.84 ± 0.14; yellow: h2 = 0.67 ± 0.19), with some evidence for covariance between the two.ConclusionsOur study supports the theoretical prediction that polymorphism should be governed by few genes of major effect, but implies broader genetic influence on variation in constituent morph traits.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0757-2) contains supplementary material, which is available to authorized users.

Chronic perfluorooctanesulfonic acid exposure disrupts lipid metabolism in zebrafish.

Perfluorooctanesulfonic acid (PFOS), a ubiquitous contaminant, has been used in various industrial applications. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism in F0 adult zebrafish and F1 offspring. Our findings revealed a severe fatty degeneration in the liver of F0 males treated with 0.5 μM PFOS and significant ultrastructure changes associated with substance transport or metabolism in liver and intestines (abnormal mitochondria and endoplasmic reticulum, disordered arrangement of inner microvilli within intracellular canaliculus). To address the potential trans-generational effects of PFOS exposure, the early gene expression related to lipid metabolism was measured by real-time quantitative polymerase chain reaction in F1 derived from chronically exposed parental fish. The results indicated that lepa (leptin α), kiss1 (kisspeptins), xdh (xanthine dehydrogenases), and insr (insulin receptor) were significantly upregulated in F1 while dgat1b (diacylglycerol O-acyltransferase), hb9 (motor neuron/pancreas homeobox), and Apoa1 (apolipoprotein A-I) were downregulated. These findings provided evidence that PFOS chronic exposure adversely impacts lipid metabolism in both F0 and F1 and demonstrated the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.

Dynamic Elastography in Diagnostics of Liver Fibrosis in Patients After Liver Transplantation Due to Cirrhosis in the Course of Hepatitis C

BackgroundAssessment of the dynamics and degree of liver fibrosis in patients after liver transplantation is a basic element in the process of determining transplant survival prognosis. It allows planning and early initiation of prophylaxis or treatment, which translates into increased chances of preventing cirrhosis and of long-term optimal function of the graft. The aim of this study was to compare the results of biopsy and dynamic elastography in diagnostics of transplanted liver fibrosis, as well as determination of the stiffness cut-off point for assessment of significant fibrosis. Patients and MethodsThe study included 36 patients who had undergone liver transplantation due to cirrhosis in the course of hepatitis C virus (HVC) infection. Fibrosis was assessed in bioptates according to the METAVIR score (F0–F4). Elastography was performed using FibroScan; receiver operating characteristic curve analysis was used to identify the cut-off point for significant fibrosis (≥F2). ResultsThe median stiffness in kPa for the whole group F0–F4 was 6.3 (range 3.4–29.9); for ≥F2 it was 6.9 (3.4–29.9), whereas for F0–F1 it was 4.4 (3.5–8.0). It was demonstrated that the value of 4.7 kPa in elastography is a statistically significant cut-off point for differentiation between the groups F0–F1 and F2–F4 (sensitivity: 93%, specificity: 57%, positive predictive value: 90%, negative predictive value: 66%), area under the receiver operating characteristic curve: 0.746 (95% confidence interval: 0.53–0.95, P < .05). ConclusionsElastography is a promising tool for noninvasive assessment of significant liver fibrosis in patients after transplantation due to cirrhosis in the course of hepatitis C; it allows reduction in the number of biopsies performed.

Hypoxia and classical activation limits Mycobacterium tuberculosis survival by Akt-dependent glycolytic shift in macrophages.

Cellular reactive oxygen species (ROS) is a major antibacterial defense mechanism used by macrophages upon activation. Exposure of Mycobacterium tuberculosis (Mtb)-infected macrophages to hypoxia is known to compromise the survival of the pathogen. Here we report that the hypoxia-induced control of intracellular Mtb load in RAW 264.7 macrophages was mediated by regulating the cellular ROS levels. We show that similar to classical activation, hypoxia incubation of macrophages resulted in decreased mitochondrial outer membrane potential (MOMP) and a concomitant increase in the cellular ROS levels. Mitochondrial depolarization and consequently higher ROS could be blocked by knocking down Akt using siRNAs, which acted by inhibiting the switch to glycolytic mode of metabolism, an essential adaptive response upon classical activation or hypoxic incubation of macrophages. Moreover, in the classically activated macrophages or in the macrophages under hypoxia incubation, supplementation with additional glucose had similar effects as Akt knockdown. Interestingly, in both the cases, the reversal of phenotype was linked with the ability of the mitochondrial F0–F1 ATP synthase activity to maintain the MOMP in the absence of oxidative phosphorylation. Both Akt knockdown and glucose supplementation were also able to rescue Mtb survival in these macrophages upon classical activation or hypoxia incubation. These results provide a framework for better understanding of how the interplay between oxygen supply, which is limiting in the human tubercular granulomas, and nutrient availability could together direct the outcome of infections in vivo.

Overexpressing F0/F1 operon of ATPase in Rhodobacter sphaeroides enhanced its photo-fermentative hydrogen production

The effect of atp genes overexpression in Rhodobacter sphaeroides HY01 on the amount of ATP, nitrogenase activity and hydrogen production were studied. The ATP content of ZTHF0 (F0 operon+), ZTHF1 (F1 operon+) and ZTHFF (F0 operon+, F1 operon+) was 6.5 ± 0.2 nmol/mL, 7.6 ± 0.2 nmol/mL and 8.3 ± 0.3 nmol/mL, respectively, which enhanced by 20.3%, 40.7%, and 53.7% compared with that of the control strain ZTH (pRK415+), respectively. However, the nitrogenase activities of ZTHF0, ZTHF1 and ZTHFF were 35.8 ± 0.5 nmol acetylene/(min·mg-dcw), 40.1 ± 0.7 nmol acetylene/(min·mg-dcw) and 29.3 ± 0.7 nmol acetylene/(min·mg-dcw), respectively, which increased by 18.2%, 32.3% and 0% compared with that of ZTH, respectively. The expression level of atp genes by real-time PCR showed that ZTHF0 or ZTHF1 only enhanced the expression of F0 operon or F1 operon, respectively, and ZTHFF enhanced the expression of both F0 and F1 operons. At the 5000 ± 200 lux with 10 mL culture, the hydrogen yields of ZTHF0 and ZTHF1 were 7636 ± 59 mL/L-culture and 8458 ± 76 mL/L, which increased by 10.5% and 27.8% compared with that of the control strain, respectively. Moreover, the maximum hydrogen evolution rate of ZTHF0 and ZTHF1 were 94.5 ± 4.1 mL/(Lh) and 103.1 ± 5.0 mL/(Lh), which enhanced by 15.4% and 20.6% compared with that of the control strain, respectively. The results suggested that overexpressing F0 operon or F1 operon could improve ATP content and hydrogen production performance in R. sphaeroides.

Clinical and laboratory characteristics of chronic hepatitis C on the early stages of development

Aim of the research – to assess the clinical and laboratory parameters in patients with chronic hepatitis C (CHC) on the early stages of development and their comparison with the level of galectin3. The study included 78 patients with oligosymptomatic course of the disease and minimal liver fibrosis in the most cases. In the most patients with stages of the disease exceeding 8 years, viral load was over a million copies/ml. In 10 % of patients on the early stages of the disease, changes corresponding to severe liver fibrosis and cirrhosis F3 and F4 were detected. Moderate correlation of ALT activity, viral load and low severity with the duration of the disease was identified. There is a trend towards a higher level of galectin3 in a long course of CHC in comparison with earlier stages of its development, with significantly higher average level of galectin-3 in patients with minimal liver fibrosis (F0–F1) as compared to advanced stages, suggesting its importance in the launching and initial mechanisms of fibrogenesis.

Structural impact of proline mutations in the loop region of an ancestral membrane protein.

The sodium ion-translocating F0 F1 ATP synthase from the bacterium Ilyobacter tartaricus contains a highly stable rotor ring composed of 11 c subunits. The synthase subunit c-in effect an 89-residue peptide that folds into a helical hairpin consisting of two membrane-spanning helices and a cytoplasmic loop-was probed for the structural impact of a series of substitutions with the β-turn-inducing proline-glycine couplet scanning the hairpin loop (residues 44-51) of the I. tartaricus sequence. We found that a Pro residue in other than the wild type position 47 alters the gross secondary structure of subunit c from α-helical to β-sheet-like, as well as changing its oligomeric ring structure, and its stability toward heat and trichloroacetic acid treatment. Such a Pro-mediated structural switch in one of the first membrane proteins in life hints to a potential evolutionary connection between α-helical and β-sheet membrane proteins.

Paternal intergenerational epigenetic response to heat exposure in male Wild guinea pigs.

Epigenetic modifications, of which DNA methylation is the best studied one, can convey environmental information through generations via parental germ lines. Past studies have focused on the maternal transmission of epigenetic information to the offspring of isogenic mice and rats in response to external changes, whereas heterogeneous wild mammals as well as paternal epigenetic effects have been widely neglected. In most wild mammal species, males are the dispersing sex and have to cope with differing habitats and thermal changes. As temperature is a major environmental factor we investigated if genetically heterogeneous Wild guinea pig (Cavia aperea) males can adapt epigenetically to an increase in temperature and if that response will be transmitted to the next generation(s). Five adult male guinea pigs (F0) were exposed to an increased ambient temperature for 2months, i.e. the duration of spermatogenesis. We studied the liver (as the main thermoregulatory organ) of F0 fathers and F1 sons, and testes of F1 sons for paternal transmission of epigenetic modifications across generation(s). Reduced representation bisulphite sequencing revealed shared differentially methylated regions in annotated areas between F0 livers before and after heat treatment, and their sons' livers and testes, which indicated a general response with ecological relevance. Thus, paternal exposure to a temporally limited increased ambient temperature led to an 'immediate' and 'heritable' epigenetic response that may even be transmitted to the F2 generation. In the context of globally rising temperatures epigenetic mechanisms may become increasingly relevant for the survival of species.

F1-ATP synthaseα-subunit: a potential target for RNAi-mediated pest management ofLocusta migratoria manilensis

The migratory locust is one of the most destructive agricultural pests worldwide. ATP synthase (F0 F1 -ATPase) uses proton or sodium motive force to produce 90% of the cellular ATP, and the α-subunit of F1 -ATP synthase (ATP5A) is vital for F1 -ATP synthase. Here, we tested whether ATP5A could be a potential target for RNAi-mediated pest management of L. migratoria. Lm-ATP5A was cloned and characterised. Lm-ATP5A is expressed in all tissues. Injection of 100 ng of the double-stranded RNA of ATP5A (dsATP5A) knocked down the transcription of the target gene and caused mortality in 1.5-5 days. The Lm-ATP5A protein level, the oligomycin-sensitive ATP synthetic and hydrolytic activities and the ATP content were correspondingly reduced following dsATP5A injection. These findings demonstrated the essential roles of Lm-ATP5A in L. migratoria and identified it as a potential target for insect pest control. © 2015 Society of Chemical Industry.

Staging of fibrosis in experimental non-alcoholic steatohepatitis by quantitative molecular imaging in rat models

ObjectivesThe aim of this study was to test the ability of hepatocyte-specific functional imaging to stage fibrosis in experimental rat models of liver fibrosis and progressive NASH. Using ROC analysis we tested the ability of a functional imaging metric to discriminate early (F1) from moderate (F2) fibrosis in the absence and presence of non-alcoholic steatohepatitis, which has not been achieved by any modality other than biopsy. MethodsGalactosyl Human Serum Albumin (GSA) was radiolabeled with the positron-emitter, 68Ga, and injected (i.v., 45–95μCi, 1.5pmol/g TBW) into 44 healthy, 19 DEN-, and 22 CDAA-treated male rats. Quantification of liver function was achieved by calculating T90, defined as the time for the liver to accumulate 90 percent of the [68Ga]GSA plateau value. All livers were excised immediately after imaging and prepared for a “blinded” histologic examination, which included fibrosis and fat content scores. Two sets of fibrosis scores were recorded for all of animals. The dominant fibrosis stage was recorded as the “Dominant Pattern” score and the “Maximum Pattern” score was assigned if a smaller distinct region with a higher fibrosis score was observed. ResultsAnimals with Dominant Pattern F0–F1 liver fibrosis (D−=39) demonstrated significantly (P<0.0001) faster accumulation of [68Ga]GSA (2.40±0.52min) than those with moderate to advanced Dominant Pattern fibrosis F2 and F4 (D+=26) (3.48±1.01min). ROC analysis (F0–F1 vs F2–F4) produced an area under the binormal curve (AUC) of 0.867±0.045. Twenty-seven of the 65 rats had small regions with higher fibrosis scores. Six of these Maximum Pattern scores reclassified the animals from D− to D+. ROC analysis of F0–F1 versus F2–F4 rats without liver fat produced AUCs of 0.881±0.053 for the Dominant Pattern Score and 0.944±0.035 for the Maximum Pattern Score. ConclusionsPET Functional Imaging of [68Ga]GSA accurately discriminates early from moderate experimental fibrosis independent of steatosis grade. If validated in human studies, molecular imaging may emerge as a potential alternative to invasive liver biopsy.

Effect of Rapid Maxillary Expansion on Voice

The purpose of this investigation is to evaluate the effect of rapid maxillary expansion (RME) on the fundamental frequency (F0) and formant frequencies F1-F4. Cross-sectional study. A total of 14 consecutive patients between the ages of 9.6 years and 15 years with a constricted maxilla undergoing RME were included in this study. Measurements were made before (T1) and after treatment (T2). These included maxillary arch length, depth, width, and perimeter in addition to F0, habitual pitch, and formants F1, F2, F3, and F4 for the vowels /ɑ/, /i/, /o/, and /u/. There was a significant difference in the mean of F1/ɑ/ and F2/ɑ/ before and after treatment (P value of 0.04 and 0.013, respectively). It is worth noting that F1/ɑ/ decreased in 11 and F2/ɑ/ decreased in 10 of the 14 subjects. The application of RME in the treatment of maxillary constriction leads to a significant lowering of the first and second formants for the vowel /ɑ/ in most subjects. Subjects undergoing rapid maxillary application should be aware of the potential change in voice quality especially in case of professional voice users.

Supervised and unsupervised separation of convolutive speech mixtures using f 0 and formant frequencies

In this paper we discuss the role of fundamental frequency f0 and formants F1, F2 and F3 of the speech signal in supervised and unsupervised source separation of real recorded convolutive speech mixtures. Initially supervised source separation is discussed where it is assumed that sources are known a priori. The supervised source separation is discussed by considering (1) only fundamental frequency f0, (2) only formants F1, F2 and F3, (3) both f0 and formants F1, F2 and F3. It is observed that last case which involves both f0 and formants gives most accurate separation results and is used as ideal case or reference to compare the separation results obtained for unsupervised source separation. The unsupervised source separation is discussed, where there is no knowledge about the sources a priori. The unsupervised source separation is discussed using (1) cross correlation of formants of different frames along with f0 and (2) standard deviation of magnitude of frequency components in F1, F2 and F3 regions of the spectrogram. It is observed that separation results obtained using both unsupervised methods are very close to the ideal case in supervised source separation. The results show that this method works better than some of the classical blind source separation algorithms like independent component analysis and non negative matrix factorization which works well only for the case of instantaneous mixtures where delay is neglected.

Acoustic radiation force impulse imaging elastography is efficacious in detecting hepatic fibrosis in children

ObjectiveTo evaluate the diagnostic performance of acoustic radiation force impulse imaging (ARFI) in detecting significant hepatic fibrosis in children. Material and methodsOur hospital's ethics committee approved the study and all patients or their representatives provided informed written consent. We included 96 children (50 boys, 46 girls; mean age, 8 years). We also studied 16 volunteers without liver disease as controls and 80 patients with diseases that can lead to fibrosis and cirrhosis of the liver. The final sample included 31 patients with biopsies and the 16 controls. All patients underwent abdominal ultrasonography including Doppler imaging and elastography with ARFI. The ARFI value, expressed as velocity (m/s) of shear wave propagation through the tissue, was calculated by averaging 16 measurements in both liver lobes. We used one-way analysis of variance to compare means between groups; we set statistical significance at P<0.05. We used Student's t-tests and chi-square tests for categorical data. ResultsThe ARFI value in children with fibrosis ≥F2 was higher (1.80±0.45m/s) than in controls and higher than in patients with F0–F1 (1.38±0.22m/s). The difference was significant (P<0.001) for detecting ≥F2. Steatosis was not related with the ARFI value (Student's t-test, P>0.84). Necroinflammatory activity was strongly associated with the ARFI value (Student's t-test, P<0.01). Fibrosis and necroinflammatory activity were strongly associated with each other (chi-square test, P<0.0001). ConclusionThe speed of shear wave propagation is significantly associated with the degree of hepatic fibrosis in children.

Non-Invasive Assessment of Liver Fibrosis Through Echosens Fibro Meter Virus

Background: Non-invasive methods for liver fibrosis assessment have replaced liver particularly for monitoring viral infections such as HBV and HCV. No studies have validated this test in NAFLD patient with high-risk factors. Methods: This study was done in patients presenting with chronic viral hepatitis B, chronic viral hepatitis C and NAFLD patient with high-risk factors whenever the necessity of liver biopsy was apparent in deciding the appropriate treatment plan. Echosens FibroMeter Virus test was done to determine the stage of fibrosis and the necroinflammatory status in this cohort of patients in a tertiary care hospital, Metro MAS in Jaipur, from September 2013 to April 2015. Results: Analysis of data from 57 patients, 24 (42%) of whom had chronic HBV infection and 7 (12%) chronic HCV infection, and 26 NAFLD patients with high risk factors (46%) was done. The median age was 50.1 12.0 (range 19–78). The mean body mass index (BMI) was 26.6 2.6 in the HBV group, 23.7 2.2 in the HCV group and 33.2 1.2 in the NAFLD group. The distribution of FibroMeter results was: F0–F1: 9 (12.2%), F1: 2 (3.3%), F1–F2: 23 (41.4%), F2: 9 (14.8%), F2–F3: 6 (11%), F3: 3 (5.0%), F3–F4: 7 (12.3%). The distribution of the necroinflammatory activity was: A0–A1: 9 (15.6%), A1–A2: 27 (47.1%), A2–A3: 21 (37.3%). No statistically significant differences were seen in this study between patients with chronic viral hepatitis and NAFLD regarding mean fibrosis scores (P = 0.468) or mean necroinflammatory activity scores (P = 0.72). Conclusion: FibroMeter Virus results should be interpreted in clinical context and potential confounding factors should be identified on a case-bycase basis. FibroMeter was also reproducible in NAFLD cohort of patients. Direct comparative study of this test with liver biopsy will further validate the sensitivity and specificity of FibroMeter test.