The diagnostic value of liver biopsy

BACKGROUND: Since the introduction of molecular diagnostic tools such as markers for hepatitis C and different autoimmune diseases, liver biopsy is thought to be useful mainly for staging but not for diagnostic purposes. The aim was to review the liver biopsies for 5 years after introduction of testing for hepatitis C, in order to evaluate what diagnostic insights – if any – remain after serologic testing. METHODS: Retrospective review of all liver biopsies performed between 1.1.1995 and 31.12.1999 at an academic outpatient hepatology department. The diagnoses suspected in the biopsy note were compared with the final diagnosis arrived at during a joint meeting with the responsible clinicians and a hepatopathologist. RESULTS: In 365 patients, 411 diagnoses were carried out before biopsy. 84.4 % were confirmed by biopsy but in 8.8 %, 6.8 % and 10.5 % the diagnosis was specified, changed or a diagnosis added, respectively. Additional diagnoses of clinical relevance were unrecognized biliary obstruction and additional alcoholic liver disease in patients with chronic hepatitis C. Liver biopsy led to change in management for 12.1 % of patients. CONCLUSION: Even in the era of advanced virological, immunological and molecular genetic testing, liver biopsy remains a useful diagnostic tool. The yield is particularly high in marker negative patients but also in patients with a clear-cut prebiopsy diagnosis, liver biopsy can lead to changes in patient management

NEFL mRNA Expression Level Is a Prognostic Factor for Early-Stage Breast Cancer Patients

Neurofilament, light polypeptide (NEFL) was demonstrated to be ectopically expressed in breast cancer tissues and decreased in lymph node metastases compared to the paired primary breast cancers in our previous study. Moreover, in several studies, NEFL was regarded as a tumor suppressor gene, and its loss of heterozygosity (LOH) was related to carcinogenesis and metastasis in several types of cancer. To explore the role of NEFL in the progression of breast cancer and to evaluate its clinical significance, we detected the NEFL mRNA level in normal breast tissues, primary breast cancer samples and lymph node metastases, and then analyzed the association between the NEFL expression level and several clinicopathological parameters and disease-free survival (DFS). NEFL mRNA was found to be expressed in 92.3% of breast malignancies and down-regulated in lymph node metastases compared to the paired primary tumors. NEFL mRNA level was lower in primary breast cancers with positive lymph nodes than in cancers with negative lymph nodes. Moreover, a low expression level of NEFL mRNA indicated a poor five-year DFS for early-stage breast cancer patients. Thus, NEFL mRNA is ectopically expressed in breast malignancies and could be a potential prognostic factor for early-stage breast cancer patients

Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease

BACKGROUND: Liver biopsy is considered the gold standard for assessing histologic lesions of non-alcoholic fatty liver disease (NAFLD). The aim was to develop and validate a new biomarker of non alcoholic steato hepatitis (NASH) the NashTest (NT) in patients with NAFLD. METHODS: 160 patients with NAFLD were prospectively included in a training group, 97 were included in a multicenter validation group and 383 controls. Histological diagnoses used Kleiner et al's scoring system, with 3 classes for NASH: "Not NASH", "Borderline", "NASH"). The area under the ROC curves (AUROC), sensitivity (Se), specificity (Sp), and positive and negative predictive values (PPV, NPV) were assessed. RESULTS: NT was developed using patented algorithms combining 13 parameters: age, sex, height, weight, and serum levels of triglycerides, cholesterol, alpha2macroglobulin, apolipoprotein A1, haptoglobin, gamma-glutamyl-transpeptidase, transaminases ALT, AST, and total bilirubin. AUROCs of NT for the diagnosis of NASH in the training and validation groups were, respectively, 0.79 (95%CI 0.69–0.86) and 0.79 (95%CI 0.67–0.87; P = 0.94); for the diagnosis of borderline NASH they were: 0.69 (95%CI 0.60–0.77) and 0.69 (95%CI 0.57–0.78; P = 0.98) and for the diagnosis of no NASH, 0.77 (95%CI 0.68–0.84) and 0.83 (95%CI 0.67–0.90; P = 0.34). When the two groups were pooled together the NashTest Sp for NASH = 94% (PPV = 66%), and Se = 33% (NPV = 81%); for borderline NASH or NASH Sp = 50% (PPV = 74%) and Se = 88% (NPV = 72%). CONCLUSION: In patients with non-alcoholic fatty liver disease, NashTest, a simple and non-invasive biomarker reliably predicts the presence or absence of NASH

Model Organisms Reveal Insight into Human Neurodegenerative Disease: Ataxin-2 Intermediate-Length Polyglutamine Expansions Are a Risk Factor for ALS

Model organisms include yeast Saccromyces cerevisae and fly Drosophila melanogaster. These systems have powerful genetic approaches, as well as highly conserved pathways, both for normal function and disease. Here, we review and highlight how we applied these systems to provide mechanistic insight into the toxicity of TDP-43. TDP-43 accumulates in pathological aggregates in ALS and about half of FTD. Yeast and fly studies revealed an interaction with the counterparts of human Ataxin-2, a gene whose polyglutamine repeat expansion is associated with spinocerebellar ataxia type 2. This finding raised the hypothesis that repeat expansions in ataxin-2 may associate with diseases characterized by TDP-43 pathology such as ALS. DNA analysis of patients revealed that intermediate-length polyglutamine expansions in ataxin-2 are a risk factor for ALS, such that repeat lengths are greater than normal, but lower than that associated with spinocerebellar ataxia type 2 (SCA2), and are more frequent in ALS patients than in matched controls. Moreover, repeat expansions associated with ALS are interrupted CAA-CAG sequences as opposed to the pure CAG repeat expansions typically associated with SCA2. These studies provide an example of how model systems, when extended to human cells and human patient tissue, can reveal new mechanistic insight into disease

Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT

Mixed-Initiative Human-Automated Agents Teaming: Towards a Flexible Cooperation Framework

The recent progress in robotics and artificial intelligence raises the question of the efficient artificial agents interaction with humans. For instance, artificial intelligence has achieved technical advances in perception and decision making in several domains ranging from games to a variety of operational situations, (e.g. face recognition [51] and firefighting missions [23]). Such advanced automated systems still depend on human operators as far as complex tactical, legal or ethical decisions are concerned. Usually the human is considered as an ideal agent, that is able to take control in case of automated (artificial) agent's limit range of action or even failure (e.g embedded sensor failures or low confidence in identification tasks). However, this approach needs to be revised as revealed by several critical industrial events (e.g. aviation and nuclear power-plant) that were due to conflicts between humans and complex automated system [13]. In this context, this paper reviews some of our previous works related to human-automated agents interaction driving systems. More specifically, a mixed-initiative cooperation framework that considers agents' non-deterministic actions effects and inaccuracies about the human operator state estimation. This framework has demonstrated convincing results being a promising venue for enhancing human-automated agent(s) teaming

The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010

<p>Abstract</p> <p>Background</p> <p>In France, it is estimated that 24% of HIV-infected patients are also infected with HCV. Longitudinal studies addressing clinical and public health questions related to HIV-HCV co-infection (HIV-HCV clinical progression and its determinants including genetic dimension, patients' experience with these two diseases and their treatments) are limited. The ANRS CO 13 HEPAVIH cohort was set up to explore these critical questions.</p> <p>To describe the cohort aims and organization, monitoring and data collection procedures, baseline characteristics, as well as follow-up findings to date.</p> <p>Methods</p> <p>Inclusion criteria in the cohort were: age > 18 years, HIV-1 infection, chronic hepatitis C virus (HCV) infection or sustained response to HCV treatment. A standardized medical questionnaire collecting socio-demographic, clinical, biological, therapeutic, histological, ultrasound and endoscopic data is administered at enrolment, then every six months for cirrhotic patients or yearly for non-cirrhotic patients. Also, a self-administered questionnaire documenting socio-behavioral data and adherence to HIV and/or HCV treatments is administered at enrolment and yearly thereafter.</p> <p>Results</p> <p>A total of 1,175 patients were included from January 2006 to December 2008. Their median age at enrolment was 45 years and 70.2% were male. The median CD4 cell count was 442 (IQR: 304-633) cells/μl and HIV RNA plasma viral load was undetectable in 68.8%. Most participants (71.6%) were on HAART. Among the 1,048 HIV-HCV chronically co-infected patients, HCV genotype 1 was predominant (56%) and cirrhosis was present in 25%. As of January, 2010, after a median follow-up of 16.7 months (IQR: 11.3-25.3), 13 new cases of decompensated cirrhosis, nine hepatocellular carcinomas and 20 HCV-related deaths were reported, resulting in a cumulative HCV-related severe event rate of 1.9/100 person-years (95% CI: 1.3-2.5). The rate of HCV-related severe events was higher in cirrhotic patients and those with a low CD4 cells count, but did not differ according to sex, age, alcohol consumption, CDC clinical stage or HCV status.</p> <p>Conclusion</p> <p>The ANRS CO 13 HEPAVIH is a nation-wide cohort using a large network of HIV treatment, infectious diseases and internal medicine clinics in France, and thus is highly representative of the French population living with these two viruses and in care.</p

Plant growth-promoting actinobacteria: a new strategy for enhancing sustainable production and protection of grain legumes

Grain legumes are a cost-effective alternative for the animal protein in improving the diets of the poor in South-East Asia and Africa. Legumes, through symbiotic nitrogen fixation, meet a major part of their own N demand and partially benefit the following crops of the system by enriching soil. In realization of this sustainability advantage and to promote pulse production, United Nations had declared 2016 as the “International Year of pulses”. Grain legumes are frequently subjected to both abiotic and biotic stresses resulting in severe yield losses. Global yields of legumes have been stagnant for the past five decades in spite of adopting various conventional and molecular breeding approaches. Furthermore, the increasing costs and negative effects of pesticides and fertilizers for crop production necessitate the use of biological options of crop production and protection. The use of plant growth-promoting (PGP) bacteria for improving soil and plant health has become one of the attractive strategies for developing sustainable agricultural systems due to their eco-friendliness, low production cost and minimizing consumption of non-renewable resources. This review emphasizes on how the PGP actinobacteria and their metabolites can be used effectively in enhancing the yield and controlling the pests and pathogens of grain legumes