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Estimating population size is particularly difficult for animal species living in concealing habitats with dense vegetation. This is the case for roe deer as for many other ungulates. Our objective was to develop a non–invasive genetic capture–mark–recapture approach based on roe deer faeces collected along transects. In a pilot study, we collected 1,790 roe deer faeces during five sampling days in a forested study area in south western Germany. We extracted DNA from 410 of these samples and carried out microsatellite analysis using seven dinucleotide markers. The analyses resulted in 328 useable consensus genotypes which were assigned to 174 individuals. The population size estimated using a Bayesian approach was 94 (82–111) male and 136 (121–156) female roe deer. Our study shows that non–invasive genetic methods are a valuable management tool for roe deer.

Introduction La périartérite noueuse (PAN) est une vascularite nécrosante intéressant les vaisseaux de moyen et de petit calibre, se manifestant habituellement sous une forme systémique. Cependant, des manifestations localisées à un seul organe ont été décrites, notamment au niveau de l’appareil génital féminin [1] . Nous rapportons ici le cas d’une patiente de 67 ans, dont le diagnostic de PAN a pu être établi grâce à l’histologie d’une masse pseudo-tumorale du fond vaginal. Observation Une patiente de 67 ans sans antécédent particulier, est hospitalisée en 2015 pour bilan de céphalées avec hyperesthésie du cuir chevelu et baisse de l’acuité visuelle de l’œil gauche dans un contexte de syndrome inflammatoire biologique. Le diagnostic d’artérite à cellules géantes est évoqué, malgré deux biopsies de l’artère temporale négatives et un TEP-scanner négatif. Une corticothérapie à 0,7 mg/kg/jour est initiée permettant une franche régression des symptômes. Parallèlement à la décroissance de la corticothérapie, le frottis cervicovaginal réalisé quelques mois plus tard met en évidence un remaniement avec atypies de signification indéterminée. La colposcopie est peu contributive et une conisation diagnostique est réalisée. L’examen anatomopathologique ne retrouve pas de dysplasie endocervicale. Un an plus tard, la patiente est cortico-dépendante à 15 mg/jour. Elle présente des métrorragies, avec à l’examen un col suspect et violacé, dur. Des biopsies successives du col sont alors pratiquées à quelques mois d’intervalle, au fur et à mesure que les lésions évoluent vers un aspect pseudo-tumoral de tout le fond vaginal et du tiers supérieur du vagin. La 1ère biopsie retrouve une muqueuse malpighienne étant le siège de lésions inflammatoires aiguës intenses avec des foyers riches en PNN, avec modification fibrinoïde de la paroi des capillaires qui est infiltrée par des PNN. La seconde biopsie met en évidence des lésions inflammatoires granulomateuses et nécrosantes avec lésions de la paroi des capillaires. Sur la 3 e biopsie, des infiltrats inflammatoires abondants apparaissent, souvent à caractère granulomateux avec éléments épithélioïdes et gigantocellulaires organisés autour d’un matériel de suppuration composé de PNN altérés avec remaniements nécrotiques et altération de la paroi des capillaires parfois nécrosée. Il n’y a jamais eu de prolifération tumorale mise en évidence. L’IRM pelvienne est normale. Un TEP-scanner est réalisé et retrouve un hypermétabolisme intense et diffus du vagin sans anomalie morphologique. Face à tous ces éléments, le diagnostic de PAN cortico-dépendante révélée par des céphalées avec localisation vaginale est évoqué. L’IRM cérébrale ne retrouve pas d’argument en faveur d’une vascularite. Un traitement par azathioprine 150 mg/jour est initié, permettant une décroissance de la corticothérapie et une amélioration stupéfiante des symptômes de la patiente. Après 2 mois de traitement, l’aspect local du vagin est inchangé, cependant la biopsie réalisée après initiation du traitement retrouve une diminution des phénomènes inflammatoires. Discussion Les cas de vascularite isolée de l’appareil génital féminin sont rares, et souvent révélées par des symptômes aspécifiques comme des métrorragies [2] . L’aspect macroscopique de cette localisation génitale de PAN était très évocateur d’une origine tumorale, ce qui a retardé le diagnostic de vascularite malgré des histologies évocatrices. C’est la répétition des biopsies et le contexte de vascularite qui a permis le diagnostic de PAN vaginale chez cette patiente. L’évolution de l’histologie sous traitement est intéressante, car si l’aspect macroscopique n’a pas évolué après deux mois de traitement, les phénomènes inflammatoires se sont quant à eux amoindris. Notons que dans d’autres cas de vascularite de l’appareil génital féminin rapportés dans la littérature, l’aspect macroscopique du col était normal [3] . Conclusion Face à une lésion pseudo-tumorale de l’appareil génital féminin, une vascularite localisée ne doit pas être méconnue, malgré la rareté de la situation. Un bilan à la recherche d’une atteinte systémique doit être réalisé, et ces patientes doivent bénéficier d’un suivi prolongé. [ABSTRACT FROM AUTHOR]

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma most reported in Asia. We performed a comprehensive clinical, pathological and genomic study of 71 European MEITL patients (36 males, 35 females, median age 67 years). The majority presented with gastrointestinal involvement and had emergency surgery, and 40% had stage IV disease. The tumors were morphologically classified into two groups: typical (58%) and atypical (i.e., non-monomorphic or with necrosis, angiotropism or starry-sky pattern) (42%), sharing a homogeneous immunophenotypic profile (CD3+ [98%] CD4- [94%] CD5- [97%] CD7+ [97%] CD8+ [90%] CD56+ [86%] CD103+ [80%] cytotoxic marker+ [98%]) with more frequent expression of TCRgd (50%) than TCRab (32%). MYC expression (30% of cases) partly reflecting MYC gene locus alterations, correlated with non-monomorphic cytology. Almost all cases (97%) harbored deleterious mutation(s) and/or deletion of the SETD2 gene and 90% had defective H3K36 trimethylation. Other frequently mutated genes were STAT5B (57%), JAK3 (50%), TP53 (35%), JAK1 (12.5%), BCOR and ATM (11%). Both TP53 mutations and MYC expression correlated with atypical morphology. The median overall survival (OS) of 63 patients (43/63 only received chemotherapy after initial surgery) was 7.8 months. Multivariate analysis found a strong negative impact on outcome of MYC expression, TP53 mutation, STAT5B mutation and poor performance status while aberrant B-cell marker expression (20% of cases) correlated with better survival. In conclusion, MEITL is an aggressive disease with resistance to conventional therapy, predominantly characterized by driver gene alterations deregulating histone methylation and JAK/STAT signaling and encompasses genetic and morphologic variants associated with very high clinical risk.

Competing Interests: Declaration of Competing Interest None.

The failure of the Fundão Dam, considered the world's largest mining disaster, released more than 55 million m 3 of ore tailings into the environment. The sediment plume formed by water and tailings spread along approximately 663 km of water bodies of the Doce River basin. It reached the Atlantic Ocean sixteen days after the dam failure. However, the effects of the dam failure in the marine coastal areas years after the disaster are still unknown. This study aims to evaluate water and sediment microbial communities of nearby coastal areas three years after the Fundão Dam failure, using 16S rRNA gene amplicon sequencing. A total of 441 samples from 25 locations were collected during two different seasons (dry and rainy). The results showed that the Doce River mouth seems to divide the microbial communities from the southern and northern stations into two groups. The plume of sediments from the Doce River seems to be impacting the marine microbiome even at the furthest sampling stations. Bacterial (Anaerolineaceae, Thermodesulfovibrionia and Rhodopirellula) and Archaeal (Bathyarchaeia and Woesearchaeia) taxa, found in high abundance in the sediment of the Doce River mouth, have been previously described in high abundance in heavy metal contaminated sediments, including the Doce River itself and in mine tailing sediments. Cyanobium, found in great abundance in the water samples from the Doce River mouth, was also reported as the most abundant in the water of the Doce River after the Fundão Dam failure. Overall, the farther from the Doce River mouth the sample was, the lower the relative abundances of these taxa were. These results provide strong evidence that the sediment plume released by the Fundão Dam failure is probably impacting the marine microbiome of nearby coastal areas, even three years after the dam failure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

T-prolymphocytic leukemia (T-PLL) is a rare T-cell neoplasm with an aggressive clinical course. Leukemic T-cells exhibit a post-thymic T-cell phenotype (Tdt - , CD1a - , CD5 + , CD2 + and CD7 + ) and are generally CD4 + /CD8 - , but CD4 + /CD8 + or CD8 + /CD4 - T-PLL have also been reported. The hallmark of T-PLL is the rearrangement of chromosome 14 involving genes for the subunits of the T-cell receptor (TCR) complex, leading to overexpression of the proto-oncogene TCL1. In addition, molecular analysis shows that T-PLL exhibits substantial mutational activation of the IL2RG-JAK1-JAK3-, STAT5B axis. T-PLL patients have a poor prognosis, due to a poor response to conventional chemotherapy. Monoclonal antibody therapy with antiCD52-alemtuzumab has considerably improved outcomes, but the responses to treatment are transient; hence, patients who achieve a response to therapy are considered for stem cell transplantation (SCT). This combined approach has extended the median survival to four years or more. Nevertheless, new approaches using well-tolerated therapies that target growth and survival signals are needed for most patients unable to receive intensive chemotherapy., Competing Interests: CONFLICTS OF INTEREST There are no conflicts of interest to report for K.L., P.L., J.S., and A.B.M.

Patients aged 80 or over with diffuse large B cell lymphoma (DLBCL) often have comorbidities that increase drug toxicity and prevent the use of otherwise optimal treatment. We performed a retrospective analysis of 43 patients aged 80 or over (median age: 83; range: 80-93) unable to receive treatment with anthracyclines, at diagnosis of DLBCL, treated with an R-CVP treatment (standard R-CHOP without doxorubicin). The patients had one or more comorbidities: 18 patients (41.9 %) had a performance status (PS) of 3; 23 patients (53.5 %) had low creatinine clearance; 12 patients (27.9 %) had low left ventricular ejection fraction; seven patients (16.3 %) had poor hepatic function; and 26 patients (60.5 %) had a Charlson index score ≥4. Thirty patients (70 %) had two or three adverse factors according to the age-adjusted International Prognostic Index. Twenty-five patients (58.1 %) received eight cycles of R-CVP, but the full eight cycles could not be given to 18 patients (41.9 %). The OR rate was 58.1 % (CR 37.2 %). There were 34 deaths (79 %) during treatment and follow-up. Ten patients (23.3 %) died early from toxicity before interim evaluation; all had PS 3. The median follow-up of surviving patients was 52.6 months. The overall 2-year survival rate was 31.9 % and the median OS was 12.6 months. The median OS for patients who completed the entire treatment was 26.4 months. The median PFS was 11.2 months. In multivariate analyses, OS was only affected by performance status ≥2 and Charlson index score ≥4. The R-CVP regimen can be active in elderly frail patients aged 80 or more with DLBCL, but systematic geriatric assessment is required so that those unsuitable for chemotherapy are excluded.

Aspergillus terreus, a saprophytic fungus, is recognized as an emerging pathogen responsible for various infections in human beings. However, bone and joint involvement is uncommon. We report a rare case of A. terreus spondylodiscitis in a 20-year-old male with a past history of recurrent, incompletely treated pulmonary tuberculosis. Clinical signs at the time of admission included cough, low-grade fever, general weakness and left-sided back pain. Histological examination of spinal biopsy samples revealed lesions of necrosis, granulomatous inflammation and septate hyphae with acute-angle branching. A. terreus was recovered from culture. The patient received antifungal therapy with voriconazole plus caspofungin and underwent surgical debridement. Further investigations revealed no cause of primary immunodeficiency such as chronic granulomatous disease, severe combined immunodeficiency syndrome or disorders of the IL-12/IFNγ signaling pathway. Moreover, HIV serological tests resulted negative and the patient was not under immunosuppressive therapy. Unfortunately, owing to precarity and medication non-adherence, vertebral sequelae occurred. This new report emphasizes the need to consider a fungal infection in patients with spondylodiscitis, regardless of the immune status.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. It is grouped with acute myeloid leukemia-related precursor neoplasms in the 2008 World Health Organization classification. Most patients with BPDCN have skin lesions at diagnosis and subsequent or simultaneous involvement of the bone marrow, peripheral blood, and lymph nodes. Patients usually respond to initial chemotherapy but often relapse. Stem cell transplantation may improve survival. This neoplasm is derived from precursors of plasmacytoid dendritic cells and is characterized by the coexpression of the immunophenotypic markers CD4, CD56, CD123, blood dendritic cell antigen-2, blood dendritic cell antigen-4, CD2AP, and lineage(-). Atypical immunophenotype expression may be present, making diagnosis difficult. BPDCN is often associated with a complex karyotype, frequent deletions of tumor suppressor genes, and mutations affecting either the DNA methylation or chromatin remodeling pathways. A better understanding of the etiology and pathophysiology of this neoplasm could open the way to new therapies targeting specific signaling pathways or involving epigenetics., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Blastic plasmacytoid dendritic cell neoplasm (LPDC) is a rare and aggressive leukemia entity with cutaneous and extracutaneous involvement, reaching most often lymph, blood and bone marrow. Two cases of LPDC diagnosed in Hospital Center of Le Mans are reported, a 78 year old woman (case 1) and a 82 year old man (case 2), and have been clinically, biologically and histologically documented. The clinical presentation, diagnostic difficulties are reminded, as well as the pathogenesis and therapeutic aspect.

Introduction: Bilobar colorectal metastases may be treated by a 2-stage surgical strategy. The risk of drop out after the first stage hepatectomy remains high and is associated with a nearly zero survival rate at 3 years. Our goal was to evaluate the factors predictive of the feasibility of the strategy and long-term survival, based on simple clinical and histologic features obtained from the first stage specimen., Patients and Methods: Patients who underwent a first stage hepatectomy with curative intent were included. Preoperative clinical parameters and histologic features of the primary neoplasm and metastases obtained at the first stage hepatectomy were analyzed and compared between patients who did or did not undergo the second stage operation. A group of comparable patients treated only by chemotherapy was used as a control group., Results: The feasibility rate of this 2-stage resection was 76% (38/50 patients). Median survival was greater in patients treated with chemotherapy alone than for those who failed the second stage. A clinicopathologic score including male sex, segment 1 metastasis, need for >3 resection(s)/radiofrequency ablation(s), vascular invasion in the primary, need for change in type of chemotherapy, and microscopic biliary invasion by the metastasis was predictive of feasibility of the second stage and disease-free survival in patients achieving the second stage., Conclusion: Combining preoperative clinical parameters with pathologic features of the primary and the metastatic lesions obtained during first stage hepatectomy predicted accurately patients who failed the second stage, and the long-term outcomes. Considering both clinical and pathologic parameters may help to define the best oncologic strategy by choosing between an exclusive chemotherapeutic or a surgical strategy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Sezary syndrome (SS) presents clinically as erythroderma, which may be pigmented, and pruritic, associated with peripheral lymphadenopathies. Erythroderma may also occur in a broad range of reactive and malignant conditions including T-cell prolymphocytic leukemia (T-PLL). We report a case initially diagnosed as SS but ultimately diagnosed as T-PLL based upon skin involvement., Case Report: A 70-year-old man was referred by his hematologist for management of SS. Physical examination revealed lymphadenopathies and mild diffuse erythema without infiltration. His WBC count was elevated at 8.3 G/L. A peripheral blood smear showed Sezary-like cells. Flow cytometry of peripheral blood revealed prolymphocytic T-cells staining positively for CD2, CD3, CD4 and CD7. Cytogenetic studies showed chromosomal abnormalities in terms of number and structure with missing chromosomes 6 and13, as well as deletion of chromosome 17. Finally, a diagnosis of T-PLL was made. Pentostatin was initiated pending treatment with alemtuzumab, but the patient's overall condition deteriorated rapidly and he died 10 days later., Discussion: Diagnosis of LPLT is based upon a number of factors. In the case presented herein, the clinically atypical nature of the skin lesions prompted the dermatologist to review the diagnosis. The morphology of the circulating T-lymphocytes and their immunologic and phenotypic characteristics finally ruled out the diagnosis of Sezary syndrome, while their association with compatible cytogenetic anomalies enabled a diagnosis of prolymphocytic leukemia to be made instead., Conclusion: Prolymphocytic leukemia involves complex differential diagnosis with regard to Sezary syndrome, posing potential pitfalls for hematologists and dermatologists., (Copyright © 2014. Published by Elsevier Masson SAS.)

Morphometry provides an objective evaluation of fibrosis in liver diseases. We developed an image analysis algorithm using automated thresholding and segmentation to separately quantify the areas and the fractal dimensions of portal-bridging fibrosis and perisinusoidal fibrosis in chronic hepatitis C liver biopsies. We studied 427 digitized liver biopsies and compared the automated measures of the different fibrosis compartments with (1) the Metavir F (fibrosis) and A (activity) histological scores, (2) the digitally assessed area of steatosis, and (3) the liver stiffness measured by elastography (Fibroscan). The perisinusoidal fibrosis area was higher than that of portal fibrosis in stages ≤F2; it reached its highest value in F2 stage and stabilized thereafter. The F3 stage was characterized by equal proportions of portal-bridging and perisinusoidal fibrosis, whereas portal-bridging area was predominant in cirrhosis. Measurement of portal-bridging fibrosis showed highly significantly different values between contiguous F stages; the ratio of portal-bridging fibrosis/perisinusoidal fibrosis displayed less overlap between Metavir stages than did the whole fibrosis area values. Fractal dimension showed that portal-bridging fibrosis tended to display a homogeneous surface-like spatial organization, whereas perisinusoidal fibrosis appeared more heterogeneous according to stage and curvilinear. The portal-bridging fibrosis area was low in cases with low Metavir activity and little steatosis, and became predominant with increasing activity and steatosis. Using stepwise multiple linear regression analysis, the liver stiffness was independently correlated to the portal-bridging fibrosis area (first step, P<0.001), the steatosis area (second step, P<0.001), and the Metavir A grade (third step, P=0.001), but not to the perisinusoidal fibrosis area. Automated quantification in a large cohort of chronic hepatitis C showed that perisinusoidal fibrosis progressively grew in early fibrosis stages but did not increase in septal or cirrhotic stages and that the portal-bridging fibrosis area appeared as a more accurate tool to assess fibrosis progression than the whole fibrosis area.

Background: Liver stiffness evaluation (LSE) by Fibroscan is now widely used to assess liver fibrosis in chronic hepatitis C. Liver steatosis is a common lesion in chronic hepatitis C as in other chronic liver diseases, but its influence on LSE remains unclear. We aimed to precisely determine the influence of steatosis on LSE by using quantitative and precise morphometric measurements of liver histology., Methods: 650 patients with chronic hepatitis C, liver biopsy, and LSE were included. Liver specimens were evaluated by optical analysis (Metavir F and A, steatosis grading) and by computerized morphometry to determine the area (%, reflecting quantity) and fractal dimension (FD, reflecting architecture) of liver fibrosis and steatosis., Results: The relationships between LSE and liver histology were better described using morphometry. LSE median was independently linked to fibrosis (area or FD), steatosis (area or FD), activity (serum AST), and IQR/LSE median. Steatosis area ≥4.0 % induced a 50 % increase in LSE result in patients with fibrosis area <9 %. In patients with IQR/LSE median ≤0.30, the rate of F0/1 patients misclassified as F ≥ 2 by Fibroscan was, respectively for steatosis area <4.0 and ≥4.0 %: 12.6 vs 32.4 % (p = 0.003). Steatosis level did not influence LSE median when fibrosis area was ≥9 %, and consequently did not increase the rate of F ≤ 3 patients misclassified as cirrhotic., Conclusion: A precise evaluation of liver histology by computerized morphometry shows that liver stiffness measured by Fibroscan is linked to liver fibrosis, activity, and also steatosis. High level of steatosis induces misevaluation of liver fibrosis by Fibroscan.

Objective: Neuroendocrine carcinomas (NECs) are rare neoplasms with an increasing incidence. Oncogenetic pathways of colorectal NEC are still poorly understood, and no treatment standards are available for these rare tumors., Methods: We analyzed retrospectively the clinical records and histology of 12 patients with colorectal NEC. KRAS and BRAF mutations were investigated after the dissection of exoendocrine and neuroendocrine components. ALK alterations and EML4-ALK transcripts were detected by in-situ hybridization and determination of fusion transcripts, respectively., Results: At the time of diagnosis, the mean age of the patients was 60 years (40-79) and 10 patients had synchronous metastases. A transient response occurred in two patients and one patient treated with cisplatin-etoposide or fluoropyrimidine-oxaliplatin, respectively. Tumor progression-related death occurred in 11 of 12 patients. Ten tumors contained an exocrine component, accounting for 5-70% of the tumor, and the other two contained an amphicrine component. BRAF/KRAS mutations were found in six of 10 tumors, corresponding to BRAF(V600E) (n=2) or KRAS(G12D) (n=2), KRAS(G12V) or KRAS(G13D). DNA was obtained from both exocrine and endocrine components in seven cases, and the BRAF/KRAS status was identical in all cases. Split of the ALK locus was detected in a minority of tumor cells in two of eight cases, but EML4-ALK transcripts were absent., Conclusion: The association of an exocrine component in all cases and the similar profile of BRAF/KRAS mutations indicate that colorectal NEC may correspond to a high-grade transformation of colorectal carcinoma. New chemotherapy regimens using targeted therapies should be assessed in these tumors.

Background and Aim: We carried out morphometric measurements of steatosis to evaluate relationships between steatosis degree and other liver lesions or metabolic syndrome components in nonalcoholic fatty liver disease (NAFLD)., Patients and Methods: We developed an algorithm to measure steatosis area. Two hundred and fourteen patients with NAFLD were included in derivation (10) and validation (204) groups. Controls consisted of patients who were steatosis-free (12), patients with chronic hepatitis C (188), and patients with alcoholic chronic liver disease (94)., Results: Accuracy of steatosis area was considered as good or very good in at least 72% of cases by three pathologists. Steatosis areas were as follows: NAFLD = 10.3 ± 9.7%, virus = 2.4 ± 3.1%, alcohol = 7.8 ± 8.2% (P<0.0001). Steatosis area was closely related to steatosis grades in NAFLD (P<0.0001 for linear trend). Steatosis area increased from the fibrosis stage F0 to the fibrosis state F2, then decreased in the stages F3 and F4 (cirrhosis) (P<0.0001 for quadratic trend). Fibrosis was present in an average steatosis area of approximately 4% (defining significant steatosis) and in nonalcoholic steatohepatitis by approximately 8% (defining severe steatosis). Steatosis and fibrosis area increased symmetrically until approximately 10%, then steatosis area decreased to null as average fibrosis area reached 32%. Average fasting glycemia (approximately 92 mg/dl) or triglycerides and BMI plateaued before a steatosis area of approximately 4%, then increased thereafter. Significant steatosis was present in 61.3% of NAFLD versus 20.2% of viral hepatitis (P<0.0001) and in 58.7% of alcoholic liver diseases (P=0.674)., Conclusions: The average threshold of steatosis area is 4% for the development of fibrosis or metabolic syndrome components and 8% for nonalcoholic steatohepatitis. Steatosis area may contribute to defining the normal range and clinical course of metabolic components.

We report the unusual case of a three-year-old girl which presented since birth a pigmented tumor of the left side 0.5cm in diameter. Surgical removal was decided given the hypothesis of a congenital naevo-cellular naevus. The histological study ended with the diagnosis of plexiform fibrohistiocytic tumor (PFHT). Two other congenital PFHT have been reported until now. PFHT is a rare mesenchymal neoplasm of intermediate malignancy, first reported by Enzinger and Zhang in 1988 which may be difficult to diagnose, because of its low frequency, particulary in congenital cases. It is important to distinguish it from others childhood cutaneous tumors (particulary plexiform neurofibroma, cellular neurothekeoma, infantile myofibromatosis, and fibrous hamartoma). The tumor has a high local recurrence rate and complete surgical resection of the tumor, with wider margins, is required., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Aims: Our aim was to develop an accurate, non-invasive, blood-test-based method for identifying the main characteristics of liver fibrosis in non-alcoholic fatty liver disease (NAFLD)., Methods: Fibrosis was staged according to NASH-CRN and Metavir systems in 226 patients with NAFLD. A fully automated algorithm measured the fractal dimension (FD) and the area of fibrosis (AOF). Independent predictors of diagnostic targets were determined using bootstrap methods., Results: (i) Development. Significant fibrosis defined by NASH-CRN F ≥2 was diagnosed by weight, glycaemia, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and prothrombin index [area under the receiver operating characteristic (AUROC)=0.867]; significant fibrosis defined by Metavir F ≥2 was diagnosed by weight, age, glycaemia, AST, ALT, ferritin and platelets (FibroMeter AUROC=0.941, P<0.005). AOF was estimated by the combination of hyaluronic acid, glycaemia, AST, ALT, platelets and prothrombin index ((a) R(2) =0.530), while FD was estimated by hyaluronic acid, glycaemia, AST/ALT, weight and platelets ((a) R(2) =0.529). (ii) Evaluation. Although NASH-CRN was a better system for fibrosis staging, Metavir staging was a better reference for blood test. Thus, the patient rate with predictive values ≥90% by tests was 97.3% with Metavir reference vs. 66.5% with NASH-CRN reference (P<10(-3)). FibroMeter showed a significantly higher AUROC than the NAFLD fibrosis score for significant fibrosis, but not for severe fibrosis or cirrhosis, with both staging systems. Relationships between fibrosis lesions were well reflected by blood tests, e.g., the correlation between histological area and FD of fibrosis (r(s) =0.971, P<10(-3)) was well reflected by the relationship between respective blood tests (r(s) =0.852, P<10(-3))., Conclusions: Different characteristics of fibrosis in NAFLD can be diagnosed and quantified by blood tests with excellent accuracy., (© 2010 John Wiley & Sons A/S.)

Neuropeptide Y (NPY) is one of the most potent stimulants of food intake in vertebrates, mammals and fish. However, the present knowledge about feeding behaviour in fish is still limited and based on studies in a few species. The Brazilian flounder Paralichthys orbignyanus is being considered for aquaculture, and it is important to understand the mechanisms regulating feeding in order to improve its performance in captivity. The objectives of this study were to clone NPY cDNA, evaluate the mRNA levels in different tissues of flounder, and also evaluate brain NPY expression to associate food intake with NPY expression levels. A 597 bp NPY cDNA was cloned from Brazilian flounder brain. NPY expression was detected in all the peripheral tissues analysed. No significant differences were observed in brain NPY gene expression over 24 h after food intake at a temperature of 15 +or- 3 degrees C. No correlation was observed among plasma glucose, total protein, cholesterol, triglycerides and NPY expression levels during this 24 h period. On the other hand, mRNA levels were increased after two weeks of fasting at elevated temperatures. Our results suggest that NPY mRNA levels in Brazilian flounder are affected by temperature.