Harmonization service and global library of models to support country-driven global information on salt-affected soils.

Global distribution of salt-affected soils (SAS) has remained at about 1 billion hectares in the literature over the years despite changes in climate, sea levels, and land use patterns which influence the distribution. Lack of periodic update of input soil data, data gaps, and inconsistency are part of the reasons for constant SAS distribution in the literature. This paper proposes harmonization as a suitable alternative for managing inconsistent data and minimizing data gaps. It developed a new harmonization service for supporting country-driven global SAS information update. The service contains a global library of harmonization models for harmonizing inconsistent soil data. It also contains models for identifying gaps in SAS database and for showing global distribution where harmonization of available data is needed. The service can be used by countries to develop national SAS information and update global SAS distribution. Its data availability index is useful in identifying countries without SAS data in the global database, which is a convenient way to identify countries to mobilize when updating global SAS information. Its application in 27 countries showed that the countries have more SAS data than they currently share with the global databases and that most of their data require SAS harmonization.

Uncinariasis: una causa poco común de hemorragia digestiva y anemia severa / Ancylostomiasis: a rare cause of gastrointestinal bleeding and severe anemia

Resumen La anemia se caracteriza por niveles bajos de hemoglobina. En Colombia, la anemia afecta al 27,7 % de la población. Las poblaciones más afectadas son los niños en edad preescolar, mujeres en edad reproductiva, embarazadas y personas de edad avanzada. Caso clínico: paciente de 58 años con cuadro clínico compatible con cor anémico, que requirió transfusión sanguínea. Mediante estudios de extensión se consideró una hemorragia digestiva por uncinariasis, por lo cual se dio un manejo antihelmíntico, con lo que tuvo buena evolución clínica y paraclínica. Discusión: hay múltiples factores de riesgo asociados con la adquisición de este parásito; se considera que esta entidad es una causa olvidada de hemorragia de vías digestivas y en algunos casos conlleva consecuencias graves como el cor anémico. El tratamiento se realiza mediante antihelmínticos, que tienen una efectividad entre el 62 % y el 92 %.

Abstract Anemia is characterized by low levels of hemoglobin. In Colombia, anemia affects 27.7% of the population. The most seriously affected populations are preschool children, women of reproductive age, pregnant women and the elderly. Clinical case: Upon admission, the 58-year-old patient was found to have a condition compatible with cardiomegaly and redistribution of blood flow and required a blood transfusion. Additional studies suggested that digestive hemorrhaging due to ancylostomiasis could be the cause. Treatment with anthelmintics was begun and had good clinical and paraclinical results. Discussion: Acquisition of this parasite, considered to be a forgotten cause of digestive bleeding, is associated with multiple risk factors. In some cases, there are severe consequences such as cardiomegaly and redistribution of blood flow. The effectiveness of treatment with anthelmintics ranges between 62% and 92%.

Differential Cell Composition and Cytokine Expression Within Lymph Node Granulomas from BCG-Vaccinated and Non-vaccinated Cattle Experimentally Infected with Mycobacterium bovis.

Cattle vaccination against bovine tuberculosis (bTB) has been proposed as a supplementary method to help control the incidences of this disease. Bacillus Calmette-Guérin (BCG) is currently the only viable candidate vaccine for immunization of cattle against bTB, caused by Mycobacterium bovis (M. bovis). In an attempt to characterize the differences in the immune response following M. bovis infection between BCG-vaccinated and non-vaccinated animals, a combination of gross pathology, histopathology and immunohistochemical (IHC) analyses was used. BCG vaccination was found to significantly reduce the number of gross and microscopic lesions present within the lungs and lymph nodes. Additionally, the microscopically visible bacterial load of stages III and IV granulomas was reduced. IHC using cell surface markers revealed the number of CD68+ (macrophages), CD3+ (T lymphocytes) and WC1+ cells (γδ T cells) to be significantly reduced in lymph node granulomas of BCG-vaccinated animals, when compared to non-vaccinated animals. B lymphocytes (CD79a+) were significantly increased in BCG-vaccinated cattle for granulomas at stages II, III and IV. IHC staining for iNOS showed a higher expression in granulomas from BCG-vaccinated animals compared to non-vaccinated animals for all stages, being statistically significant in stages I and IV. TGFß expression decreased alongside the granuloma development in non-vaccinated animals, whereas BCG-vaccinated animals showed a slight increase alongside lesion progression. IHC analysis of the cytokines IFN-γ and TNF-α demonstrated significantly increased expression within the lymph node granulomas of BCG-vaccinated cattle. This is suggestive of a protective role for IFN-γ and TNF-α in response to M. bovis infection. Findings shown in this study suggest that the use of BCG vaccine can reduce the number and severity of lesions, induce a different phenotypic response and increase the local expression of key cytokines related to protection.

Accuracy of immunoassay and mass spectrometry urinary free cortisol in the diagnosis of Cushing's syndrome.

PURPOSE: Urinary free cortisol (UFC) determination by highly specific methods as mass spectrometry instead of commercially available antibody-based immunoassays is increasingly recommended. However, clinical comparisons of both analytical approaches in the screening of Cushing's syndrome (CS) are not available. The aim of this study was to evaluate the diagnostic value of mass spectrometry versus immunoassay measurements of 24 h-UFC in the screening of CS. METHODS: Cross-sectional study of 33 histologically confirmed CS patients: 25 Cushing's disease, 5 adrenal CS and 3 ectopic CS; 92 non-CS patients; and 35 healthy controls. UFC by immunoassay (UFCxIA) and mass spectrometry (UFCxMS), urinary free cortisone (UFCo) and UFC:UFCo ratio were measured, together with creatinine-corrected values. Sensitivity, specificity, AUC and Landis and Koch concordance index were determined. RESULTS: AUC for UFCxIA and UFCxMS were 0.77 (CI 0.68-0.87) and 0.77 (CI 0.67-0.87) respectively, with a kappa coefficient 0.60 and strong Landis and Koch concordance index. The best calculated cutoff values were 359 nmol/24 h for UFCxIA (78 % sensitivity, 62 % specificity) and 258.1 nmol/24 h for UCFxMS (53 % sensitivity, 86 % specificity). The upper limit of UFCxIA and UCFxMS reference ranges were 344.7 and 169.5 nmol/24 h respectively. Sensitivity and specificity for CS diagnosis at these cutpoints were 84 and 56 % for UFCxIA and 81 and 54 % for UFCxMS. CONCLUSIONS: According to our data, both methods present a very similar diagnostic value. However, results suggest that lower cutoff points for mass spectrometry may be necessary in order to improve clinical sensitivity.

Neutrophil gelatinase-associated lipocalin is a biomarker of acute-on-chronic liver failure and prognosis in cirrhosis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a syndrome that occurs in cirrhosis characterized by organ failure(s) and high mortality rate. There are no biomarkers of ACLF. The LCN2 gene and its product, neutrophil gelatinase-associated lipocalin (NGAL), are upregulated in experimental models of liver injury and cultured hepatocytes as a result of injury by toxins or proinflammatory cytokines, particularly Interleukin-6. The aim of this study was to investigate whether NGAL could be a biomarker of ACLF and whether LCN2 gene may be upregulated in the liver in ACLF. METHODS: We analyzed urine and plasma NGAL levels in 716 patients hospitalized for complications of cirrhosis, 148 with ACLF. LCN2 expression was assessed in liver biopsies from 29 additional patients with decompensated cirrhosis with and without ACLF. RESULTS: Urine NGAL was markedly increased in ACLF vs. no ACLF patients (108(35-400) vs. 29(12-73)µg/g creatinine; p<0.001) and was an independent predictive factor of ACLF; the independent association persisted after adjustment for kidney function or exclusion of variables present in ACLF definition. Urine NGAL was also an independent predictive factor of 28day transplant-free mortality together with MELD score and leukocyte count (AUROC 0.88(0.83-0.92)). Urine NGAL improved significantly the accuracy of MELD in predicting prognosis. The LCN2 gene was markedly upregulated in the liver of patients with ACLF. Gene expression correlated directly with serum bilirubin and INR (r=0.79; p<0.001 and r=0.67; p<0.001), MELD (r=0.68; p<0.001) and Interleukin-6 (r=0.65; p<0.001). CONCLUSIONS: NGAL is a biomarker of ACLF and prognosis and correlates with liver failure and systemic inflammation. There is remarkable overexpression of LCN2 gene in the liver in ACLF syndrome. LAY SUMMARY: Urine NGAL is a biomarker of acute-on-chronic liver failure (ACLF). NGAL is a protein that may be expressed in several tissues in response to injury. The protein is filtered by the kidneys due to its small size and can be measured in the urine. Ariza, Graupera and colleagues found in a series of 716 patients with cirrhosis that urine NGAL was markedly increased in patients with ACLF and correlated with prognosis. Moreover, gene coding NGAL was markedly overexpressed in the liver tissue in ACLF.

Early non-invasive selection of patients at high risk of severe hepatitis C recurrence after liver transplantation.

BACKGROUND: The early identification of patients at high risk of severe post liver transplant hepatitis C recurrence is relevant, as these patients may be treated using interferon (IFN)-free regimens. METHODS: In a retrospective study with prospectively collected data, we investigated whether the use of several non-invasive methods (fibrosis 4 index [FIB-4], AST-to-platelets ratio index [APRI], enhanced liver fibrosis test [ELF], IFN-γ-inducible protein 10 [IP-10], and transient elastography by Fibroscan) and their combinations 6 months after transplantation could identify those recipients at higher risk of severe recurrence, defined by the presence of significant fibrosis (F ≥2) and/or portal hypertension (hepatic venous pressure gradient ≥6 mmHg) 12 months after transplant. Seventy-two hepatitis C virus (HCV)-infected liver transplant patients and 10 recipients in whom HCV was eradicated before transplantation were included in the study. RESULTS: The levels of all biomarkers were significantly higher in HCV-infected recipients than in controls. Among HCV recipients, levels of biomarkers were significantly higher in patients with severe recurrence. Although there were no statistically significant differences between biomarkers, APRI, ELF, and FIB-4 obtained the highest area under the ROC curve values. The combination of serum biomarkers with Fibroscan increased the negative and positive predictive values, although diagnostic accuracy of individual tests was not significantly improved. CONCLUSIONS: Patients at higher risk of severe HCV recurrence can be identified early, 6 months after transplantation, using readily available non-invasive methods.

Non-tuberculous mycobacteria in wild boar (Sus scrofa) from Southern Spain: epidemiological, clinical and diagnostic concerns.

Non-tuberculous mycobacteria (NTM) are widely distributed in the environment, particularly in wet soil, marshland, rivers or streams, but also are causative agents of a wide variety of infections in animals and humans. Little information is available regarding the NTM prevalence in wildlife and their effects or significance in the bovine tuberculosis (bTB) epidemiology and diagnosis. This research shows the most frequently NTM isolated in lymph nodes of wild boar (Sus scrofa) from southern Spain, relating the NTM presence with the individual characteristics, the management of animals and the possible misdiagnosis of Mycobacterium bovis in concurrent infections. A total of 219 NTM isolates were obtained from 1249 wild boar mandibular lymph nodes sampled between 2007 and 2011. All but 75 isolates were identified by the PCR-restriction analysis-hsp65, and a partial sequencing of the 16S rDNA was carried out to identify the rest of the isolates. Results showed that Mycobacterium chelonae was the most frequently isolated NTM specie (133 isolates, 60.7%), followed by Mycobacterium avium (24 isolates, 11%). No relation was found regarding sex, body condition and management, but M. chelonae was more frequently detected in adults, whereas M. avium was more prevalent in subadults. The high NTM prevalence observed in the studied wild boar populations could make difficult the bTB diagnostic.

Influence of porcine circovirus type 2 infections on bovine tuberculosis in wild boar populations.

The wild boar is an important reservoir of bovine tuberculosis (bTB) in south-western Spain. Some risk factors such as wild boar density or age have been associated with the presence of high prevalences of bTB in wild boar. However, the influence of other risk factors such as co-infections with other pathogens has not yet been studied. This work aims to assess the influence of porcine circovirus type 2 (PCV-2) infection on bTB prevalence and bTB lesional patterns observed in wild boar. The presence of bTB-like lesions was evaluated in 551 hunted wild boar from 11 different game estates in south-western Spain, with a known history of bTB. Tuberculosis prevalences in each estate were calculated based on the percentage of animals found with bTB-like lesions. The percentage of animals with generalized bTB lesional patterns (bTB lesions in more than one organ) was also assessed. The prevalence of PCV-2 was studied in each estate using a specific PCR assay. The relationship between PCV-2 and bTB prevalences and between PCV-2 infections and the presence of generalized lesional patterns in wild boar were analysed. A statistical relationship between the prevalences of bTB and PCV-2 was found, with bTB prevalences being higher in estates where prevalences of PCV-2 were high. On the other hand, animals infected with PCV-2 were more likely to develop a generalized lesional pattern. Porcine circovirus type 2 prevalences seem to be associated with prevalences of bTB in wild boar. PCV-2 infection may aggravate the development and severity of bTB, favouring the presence of generalized lesional patterns and raising the risk of contagion in these estates. The implementation of sanitary measures that focus on the control of PCV-2 infection may be necessary as a preliminary measure in bTB control programmes for wild boar.

Immunopathology of granulomas produced by Mycobacterium bovis in naturally infected wild boar.

Limited information has been published on the wild boar immune response against bovine tuberculosis (bTB) and the immunopathogenesis of the pathological hallmark (granuloma) in this species. The main objectives of this study were, on the one hand, to characterize the histopathological features (number of acid-fast bacilli (AFB) and multinucleated giant cells (MNGCs) and the immunohistochemical distribution of different cell subsets (CD3+, CD79a+ and MAC387+) and chemical mediators (iNOS and IFN-γ) in the different developmental stages of granulomas produced by the natural infection of Mycobacterium bovis (M. bovis) in wild boar. On the other hand, the study also aimed to analyze the mechanisms underlying the marked differences in the typical lesional patterns observed in M. bovis infections of wild boar (contained, not generalized) and those previously described in fallow deer (poorly contained, generalized). The majority of granulomas analyzed (95.3%) did not show any AFB with the ZN stain and a low number of MNGCs were identified in the different granuloma stages. The immunohistochemical analysis showed that MAC387 was the only immune marker that produced decreasing positivity by granuloma stage, being statistically significantly lower in stages III and IV when compared to stage I and II. Immune markers for lymphocyte cells (CD3 and CD79a) showed a slight rise in the positivity (which was not statistically significant) in the advanced granuloma stages. In keeping with the presence of large numbers of T cells and macrophages, there was a consistently high level of expression of IFN-γ at all stages of granuloma development without a statistical significant decrease in advanced stages. Also related with the higher presence of macrophages in stage I and II, the expression of iNOS was higher in early stages and sustained until stage III, showing a non statistical significant decrease in stage IV. The macrophage and iNOS activity are more intense and sustained along the granuloma development than those described in fallow deer. Immunohistochemical protocols with a panel of markers for wild boar different cells subsets (CD3+, CD79a+ and MAC387+) and chemical mediators (iNOS and IFN-γ), and their use to further investigate the immune response in this species are provided.

The role of VEGFR-2 expression in outcomes and survival of patients with peritoneal carcinomatosis from appendiceal cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a prognostic factor and target treatment for metastatic colorectal and ovarian cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival on peritoneal carcinomatosis (PC) from appendiceal cancer. We hypothesize that tumoral high expression of VEGF receptor 2 (VEGFR-2) is a negative prognostic factor for survival in patients with PC from appendiceal cancer. METHODS: A retrospective study of a prospective database revealed 89 patients with PC from appendiceal cancer who underwent 127 CRS/HIPECs. Surgical specimens from 59 patients were tested to identify high vs. low VEGFR-2 expression. Patient outcomes and survival were analyzed. RESULTS: There were 26 males and 33 females. Mean age was 51 years. Forty-seven VEGFR-2 high expressers and 15 low expressers were identified. Mean follow-up of high and low expressers was 25.1 and 26.6 months, respectively (p = 0.806). At follow-up, 33 (70%) high expressers were alive and 14 (30%) deceased, while 11 (92%) low expressers were alive and 1 (8%) deceased. Recurrence, use of bevacizumab, CC score, PCI, and LN status showed no differences between high and low expressers. OS for high expressers was 90.5%, 59.8%, and 47.1% at 1-, 3-, and 5-years, respectively, while OS for low expressers remained stable at 91.7% at 1-, 3-, and 5-years (p = 0.133). CONCLUSION: There is a trend towards better outcomes and survival in patients with PC from appendiceal cancer who have low expression of VEGFR-2 compared to high expression. More studies are encouraged to confirm this trend.

Repeated cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from appendiceal cancer: analysis of survival outcomes.

BACKGROUND: Cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC) is the procedure of choice in patients with peritoneal dissemination from appendiceal cancer. Although recurrence rates are 26%-44% after first CRS/HIPEC, the role of repeated CRS/HIPEC has not been well defined. We hypothesize that patients undergoing multiple CRS/HIPEC's have meaningful long term survival. METHODS: A retrospective study of a prospective database of 294 patients with peritoneal carcinomatosis (PC) was conducted, of these 162 had PC of appendiceal origin. Twenty-six of these patients underwent 56 CRS/HIPEC. Survival and outcomes was analyzed. RESULTS: The percentage of patients with pre-surgical PCI scores ≥ 20 for the first, second, and third CRS/HIPEC was 65, 65, and 25%, respectively. Complete cytoreduction (CC 0-1) at first, second, and, third surgeries was 96, 65 and 75%, respectively. The mean operating time was 10.1 h. There was no 30-day peri-operative mortality. Following the first, second, and third CRS/HIPEC 27, 42, and 50% experienced grade III complications, respectively. Mean follow up was 51, 28, and 16 months from the first, second, and third CRS/HIPEC, respectively. Overall survival rate for the first CRS/HIPEC was 100, 83, 54, and 46% at years 1, 3, 5 and 10, respectively; from the second CRS/HIPEC 91, 53, and 34% at 1, 3, and 5 years, respectively; and from the third CRS/HIPEC was 75% at one year. CONCLUSION: Repeat CRS/HIPEC can lead to meaningful long term survival rates in patients with appendiceal peritoneal carcinomatosis with morbidity and mortality similar to those of the initial CRS/HIPEC.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial ovarian carcinoma: upfront therapy, at first recurrence, or later?

AIM: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) has been proposed as treatment for advanced epithelial ovarian carcinoma (EOC). No consensus exists on when to administer CRS+HIPEC during the natural history of the disease, namely, as upfront therapy, at first recurrence, or at second or subsequent recurrence. PATIENTS AND METHODS: We analyzed a series of patients with advanced EOC collected prospectively in an institution with a peritoneal malignant disease treatment program. Patients were treated with CRS+HIPEC upfront, at first recurrence, and at second or subsequent recurrence. RESULTS: We treated 42 patients: 15 upfront, 19 at first recurrence, and 8 at second or subsequent recurrence. Cytoreduction was complete (CC0) in 75% of cases; residual disease was <2.5 mm (CC1) in 25%. Severe morbidity (CTCAE v.3.0, grade 3-4) was 26%, and hospital mortality was 7%. After a median follow-up of 24 months, median overall survival was 77.8 months for patients treated upfront, 62.8 months for patients treated at first recurrence, and 35.7 months for patients treated at second or subsequent recurrence. Disease-free survival was 21.1 months, 18 months, and 5.7 months, respectively. Overall survival in the upfront and first recurrence groups was similar, and statistically significant differences with the second recurrence group were identified (p<0.03). CONCLUSIONS: Treatment of advanced EOC using CRS+HIPEC is promising in terms of overall survival and disease-free survival when administered as upfront and at first recurrence therapy. These results warrant further evaluation in a randomized trial.

Reducing Eurasian wild boar (Sus scrofa) population density as a measure for bovine tuberculosis control: effects in wild boar and a sympatric fallow deer (Dama dama) population in Central Spain.

Research on management of bovine tuberculosis (bTB) in wildlife reservoir hosts is crucial for the implementation of effective disease control measures and the generation of practical bTB management recommendations. Among the management methods carried out on wild species to reduce bTB prevalence, the control of population density has been frequently used, with hunting pressure a practical strategy to reduce bTB prevalence. However, despite the number of articles about population density control in different bTB wildlife reservoirs, there is little information regarding the application of such measures on the Eurasian wild boar (Sus scrofa), which is considered the main bTB wildlife reservoir within Mediterranean ecosystems. This study shows the effects of a management measure leading to a radical decrease in wild boar population density at a large hunting estate in Central Spain, in order to assess the evolution of bTB prevalence in both the wild boar population and the sympatric fallow deer population. The evolution of bTB prevalence was monitored in populations of the two wild ungulate species over a 5-year study period (2007-2012). The results showed that bTB prevalence decreased in fallow deer, corresponding to an important reduction in the wild boar population. However, this decrease was not homogeneous: in the last season of study there was an increase in bTB-infected male animals. Moreover, bTB prevalence remained high in the remnant wild boar population.

Comparative pathology of the natural infections by Mycobacterium bovis and by Mycobacterium caprae in wild boar (Sus scrofa).

The potential role of wild animals in the maintenance and spread of tuberculosis (TB) infection in domestic livestock is of particular importance in countries where eradication programs have substantially reduced the incidence of bovine tuberculosis but sporadic outbreaks still occur. Mycobacterium bovis is the agent mainly isolated in wildlife in Spain, but recently, infections by Mycobacterium caprae have increased substantially. In this study, we have analysed 43 mandibular lymph nodes samples containing TB-like lesions from 43 hunted wild boar from Madrid and Extremadura (central and south-western regions of Spain). After isolation, identification and typing of Mycobacterium tuberculosis complex isolates, we found that 23 mandibular lymph nodes involved M. caprae infections and 20 M. bovis. The lesions were compared for histopathology (different granuloma stage and number of multinucleated giant cells (MNGCs)), and acid-fast bacilli (AFBs) were quantified in the Ziehl-Neelsen-stained slides. Granulomas produced by M. caprae showed more stage IV granulomas, more MNGCs and higher AFBs counts than those induced by M. bovis. In conclusion, lesions caused by M. caprae would be more prone to the excretion of bacilli, and infected animals result as a high-risk source of infection for other animals.

Adenoviral dominant-negative soluble PDGFRß improves hepatic collagen, systemic hemodynamics, and portal pressure in fibrotic rats.

BACKGROUND & AIMS: Platelet-derived growth factor (PDGF) is the most potent stimulus for proliferation and migration of stellate cells. PDGF receptor ß (PDGFRß) expression is an important phenotypic change in myofibroblastic cells that mediates proliferation and chemotaxis. Here we analyzed the relationship between PDGFRß expression, hemodynamic deterioration, and fibrosis in CCl(4)-treated rats. Thereafter, we investigated the effects produced by an adenovirus encoding a dominant-negative soluble PDGFRß (sPDGFRß) on hemodynamic parameters, PDGFRß signaling pathway, and fibrosis. METHODS: Mean arterial pressure, portal pressure, PDGFRß mRNA expression, and hepatic collagen were assessed in 6 controls and 21 rats induced to hepatic fibrosis/cirrhosis. Next, 30 fibrotic rats were randomized into three groups receiving iv saline and an adenovirus encoding for sPDGFRß or ß-galactosidase. After 7days, mean arterial pressure, portal pressure, serum sPDGFRß, and hepatic collagen were measured. RESULTS: CCl(4)-treated animals for 18weeks showed a significantly higher increase in PDGFRß mRNA compared to those treated for 13weeks and control rats. In CCl(4)-treated rats, the fibrous tissue area ranged from moderate to severe fibrosis. A direct relationship between the degree of fibrosis, hemodynamic changes, and PDGFRß expression was observed. Fibrotic rats transduced with the adenovirus encoding sPDGFRß showed increased mean arterial pressure, decreased portal pressure, lower activation of the PDGFRß signaling pathway, and reduced hepatic collagen than fibrotic rats receiving ß-galactosidase or saline. CONCLUSIONS: PDGFRß activation closely correlates with hemodynamic disorders and increased fibrosis in CCl(4)-treated rats. Adenoviral dominant negative soluble PDGFRß improved fibrosis. As a result, the hemodynamic abnormalities were ameliorated.

Histological and immunohistochemical characterisation of Mycobacterium bovis induced granulomas in naturally infected fallow deer (Dama dama).

Mycobacterium bovis infections in fallow deer have been reported in different countries and play an important role in the epidemiology of bovine tuberculosis (bTB), together with other deer species. There is little knowledge of the pathogenesis of bTB in fallow deer. The aim of this study was to perform a histopathological characterisation of the granulomas induced by M. bovis in this species and the immunohistochemical distribution of different cell subsets (CD3+, CD79+, macrophages) and chemical mediators (iNOS, TNF-α, IFN-γ) in the different developmental stages of granulomas. Stage I/II granulomas showed a marked presence of macrophages (MAC387+) expressing high iNOS levels while stage III/IV granulomas showed a decrease in the number of these cells forming a rim surrounding the necrotic foci. This was correlated with the presence of IFN-γ expressing cell counts, much higher in stage I/II than in stage III/IV. The number of B cells increased alongside the developmental stage of the granuloma, and interestingly the expression of TNF-α was very low in all the stages. This characterisation of the lesions and the local immune response may be helpful as basic knowledge in the attempts to increase the vaccine efficacy as well as for disease severity evaluation and for the development of improved diagnostic tools. Immunohistochemical methods using several commercial antibodies in fallow deer tissues are described.

Assessment of liver fibrosis before and after antiviral therapy by different serum marker panels in patients with chronic hepatitis C.

BACKGROUND: Liver biopsy is the reference standard to assess liver fibrosis in chronic hepatitis C. AIM: To validate and compare the diagnostic performance of non-invasive tests for prediction of liver fibrosis severity and assessed changes in extracellular matrix markers after antiviral treatment. METHODS: The performances of Forns' score, AST to platelet ratio index (APRI), FIB-4 index and Enhanced Liver Fibrosis (ELF) score were validated in 340 patients who underwent antiviral therapy. These scores were determined 24 weeks after treatment in 161 patients. RESULTS: Forns' score, APRI, FIB-4 and ELF score showed comparable diagnostic accuracies for significant fibrosis [area under the receiver operating characteristic curve (AUROC) 0.83, 0.83, 0.85 and 0.81, respectively]. To identify cirrhosis, FIB-4 index showed a significantly better performance over APRI and ELF score (AUROC 0.89 vs. 0.83 and 0.82, respectively). ELF score decreased significantly in patients with sustained virological response (SVR) (P < 0.0001) but remained unchanged in nonresponders. Non-1 hepatitis C virus (HCV) genotype, baseline lower HCV RNA, glucose, hyaluronic acid and higher cholesterol levels were independently associated with SVR. CONCLUSIONS: Simple panel markers and ELF score are accurate at identifying significant fibrosis and cirrhosis in chronic hepatitis C. A decrease in ELF score after antiviral treatment reflects the impact of viral clearance in hepatic extracellular matrix and probably in the improvement of liver fibrosis.