Horiba Yumizen hematology analysers minimize microscopy slide reviews

Horiba has recently announced the publication of scientific studies which demonstrate the excellent performance of its new HELO high throughput fully automated hematology platform on body fluid and pathological samples. Horiba’s Yumizen® H2500 and H1500 automated hematology analysers within the HELO platform deliver enhanced precision for complete blood counts and white blood cell (WBC) differential testing, with body fluid analysis included as standard. This improves diagnosis, minimizes unnecessary manual microscopy slide reviewing and enhances laboratory workflow, as highlighted by two recent scientific evaluation studies.
The first study was undertaken by Nantes University Hospital (CHU de Nantes) focusing on the need for automated analysis of biological fluids for robust and reliable results reporting. Hematological analysis of body fluids (BF) can provide clinicians with valuable diagnostic information as it can indicate a number of serious medical conditions. Manual microscopy has traditionally been used to determine total and differentiated WBC in BFs, however, results can be affected by inter-operator variability and take time to undertake. By using an automated method of analysis of WBC in a body fluid smear, this can improve turnaround times and accuracy.
To ensure the robustness and reliability of automated BF analysis in routine laboratory workflows, the evaluation study was undertaken on the performance of the automated body fluid analysis cycle on the Yumizen H2500. The study included 98 samples from cerebro-spinal, pleural, ascitic, pericardic and bronchoalveolar liquid (BAL) fluids which were used for comparative leukocyte and erythrocyte counts, as well as differential. This confirmed the good analytical performance of Yumizen analyser in comparison with conventional microscopic count, as well as a reference analyser.
The second study explored the flagging efficiency of the new analyser. Pathological samples, coming from patients with altered hematopoiesis, often trigger a WBC-Diff flag; this is due to poor cell separation and requires a manual slide review (MSR) by microscopy to confirm the WBC differential. Laboratory workload would be optimized if MSR could be reduced without compromising patient care. Therefore, the study undertaken by the Institut Bergonié Comprehensive Cancer Centre compared the flagging performance in the WBC differential of the Yumizen H1500/H2500 to a routine analyser. This included patients with pathology or treatment affecting hematopoiesis, such as those undergoing chemotherapy or with onco-hematologic disorders.
The study on 228 pathological samples (100 from patients on chemotherapy for solid tumours and 128 from patients with malignant blood disease) demonstrated an improvement in the WBC-diff analysis and reliability of the Yumizen H1500/2500 analyser compared to a routine analyser. It delivered better precision and specificity, due to improved cell separation, and a significant decrease (-21%) in unnecessary morphology reviewing by microscopy, thus saving significant time in the laboratory.
Commenting on the successful outcome of the studies, Mandy Campbell, Horiba Medical said, “These evaluation studies undertaken by recognized authorities in hematological analysis, demonstrate the excellent performance of our new Yumizen H1500/H2500 automated hematology analysers with both body fluid and pathological samples. Body fluid analysis is available as standard on these analysers which have been shown to enhance diagnoses and lower film review rates to improve laboratory workflow.” www.horiba.com/medical

Zika virus study reveals possible causes of brain pathology

In healthy individuals, the Zika virus causes flu-like symptoms. If a pregnant woman becomes infected, the unborn child can suffer from severe brain abnormalities as a result of mechanisms that have not yet been explained. A study by the Technical University of Munich (TUM) and the Max Planck Institute of Biochemistry (MPI-B) shows that Zika virus proteins bind to cellular proteins that are required for neural development.

A few years ago, Zika virus spread across South America, posing a health issue with global impact. A significant number of South American women who came into contact with the virus for the first time at the start of their pregnancy by a mosquito bite subsequently gave birth to children with severe disabilities. The babies suffered from a condition known as microcephaly; they were born with a brain that was too small. This can lead to intellectual disabilities and other serious neurological disorders.

Scientists succeeded in proving that these deformities are caused by Zika virus infections, but so far they have been unable to explain why. Andreas Pichlmair, Chair for Viral Immunopathology at TUM and his team from the TUM Institute of Virology and MPI-B have examined how Zika virus influences human brain cells. They identified the virus proteins with the potential to affect neuronal development in the developing brain.

 “Zika virus is closely related to the Hepatitis C virus and certain tropical diseases such as Dengue and West Nile virus. It is, however, the only virus that causes brain damage in newborns,” explains Pichlmair, who headed the recent study.

The researchers discovered that the virus uses certain cellular proteins to replicate its own genome. These molecules are also important neurological factors in the process of a stem cell developing into a nerve cell. “Our findings suggest that the virus takes these factors away from brain development and uses them to replicate its genome, which prevents the brain from developing properly,” explains the virologist.

When the team headed by Pichlmair removed the factors in the cells, the virus found it much harder to replicate. The researchers were able to demonstrate which virus proteins come in contact with these development factors and cause the brain defects. “Previous studies revealed the virus proteins necessary for the packaging or replication of the viral genome but it was enigmatic to understand how these proteins influence neuronal development. It appears that viral proteins are responsible for causing the serious defects in the unborn – unintentionally we presume,” says Pichlmair.

In their comprehensive proteomics survey, the research team identified cellular proteins that were altered chemically or numerically by the virus or which bound to virus proteins. In this way, they were not only able to illustrate possible reasons for the caused deformities, but also obtained a very clear picture of how the virus reprograms the cell to use it for its own replication. www.tum.de/nc/en/about-tum/news/press-releases/details/34920/

Astell Scientific at Medica

Astell Scientific is a world renowned manufacturer and supplier of steam sterilizers. Astell Scientific autoclaves, steam generators and effluent decontamination systems (EDS) are designed to meet the exacting demands of modern Laboratory, Research and Medical professionals, and as such incorporate innovations such as colour touchscreen controllers as standard throughout the range.

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All Astell autoclaves are manufactured in accordance with standards and directives including ISO 9001:2015, Pressure Equipment Directive (PED 2014/68/EU) and CE (Conformité Européenne).www.astell.com

Oncimmune at Medica

The battle against cancer hinges on the early detection and then delivery of effective treatment. Oncimmune is working to revolutionise both the detection of cancer and its treatment by harnessing the sophisticated disease-detecting capabilities of the immune system to find cancer in its early stages. Oncimmune’s range of diagnostic tests assist clinicians to identify the presence of cancer on average four years before standard clinical diagnosis, whilst its technology platform and sample biobanks are helping healthcare companies to develop new cancer treatments.

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Jackson ImmunoResearch at Medica

Jackson ImmunoResearch manufactures secondary antibodies and conjugates, with an outstanding reputation for quality, earned over 30 years. Our products are used in Western Blotting, IHC/ICC/IF, Flow Cytometry, ELISA, Electron Microscopy and many other immunological techniques. From our UK office we serve Europe with euro pricing, technical service and fast delivery. www.jacksonimmuno.com

Starna Scientific at Medica

Starna, established 1964, has a worldwide reputation for quality, service and innovation in the production and supply of spectrophotometer cells, optical components and Certified Reference Materials (CRMs). World-leader with over 50 years’ experience in the production of Certified Reference Materials for UV-Vis-NIR & Fluorescence spectroscopy; it is the only company to achieve both ISO/IEC 17025 and ISO 17034 for this range of products. A highly regarded manufacturer of high precision quartz and glass Cells/Cuvettes for Photometers and Fluorimeters. Starna sells worldwide to instrument manufacturers, pharmaceuticals, life-biosciences, R&D laboratories, medical companies and universities.

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GAMBICA at Medica

GAMBICA is the Trade Association for Instrumentation, Control, Automation and Laboratory Technology in the UK. Our insight and influence help our members to be more competitive by increasing their knowledge and impact. Together we remove barriers and maximise the market potential in our industry.
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Scientists develop test for uncommon brain diseases

National Institutes of Health (NIH) scientists have developed an ultrasensitive new test to detect abnormal forms of the protein tau associated with uncommon types of neurodegenerative diseases called tauopathies.  This advance gives them hope of using cerebrospinal fluid, or CSF – an accessible patient sample – to diagnose these and perhaps other, more common neurological diseases, such as Alzheimer’s disease.

Scientists have linked the abnormal deposition of tau in the brain to at least 25 different neurodegenerative diseases. However, to accurately diagnose these diseases, brain tissue often must be analysed after the patient has died. For their study, the researchers used the same test concept they developed when using postmortem brain tissue samples to detect the abnormal tau types associated with Pick disease, Alzheimer’s disease and chronic traumatic encephalopathy (CTE). They adapted the test to use CSF for the detection of abnormal tau of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and other less common tauopathies.

They detected abnormal tau in CSF from both living and deceased patients. In one case, the test led to a corrected diagnosis in a patient who had died from CBD, but who was initially diagnosed with PSP. The new test is called 4R RT-QuIC – which stands for 4-repeat tau protein amplified in a real-time, quaking-induced conversion process.

The researchers plan to continue evaluating the clinical performance of 4R RT-QuIC by analysing larger sets of CSF samples. One focus will be to compare test results from tauopathy patients who agree to provide CSF samples both before and after death. The scientists hope this type of evaluation will help them better understand how abnormal tau in CSF evolves during brain disease.

NIHwww.niaid.nih.gov/news-events/nih-scientists-develop-test-uncommon-brain-diseases

Researchers develop method for identifying aggressive breast cancer drivers

Precision cancer medicine requires personalized biomarkers to identify patients who will benefit from specific cancer therapies. In an effort to improve the accuracy of predictions about prognosis for patients with breast cancer and the efficacy of personalized therapy, University of North Carolina Lineberger Comprehensive Cancer Center researchers have developed a method to precisely identify individual patients who have aggressive breast cancer. The new approach involves sorting and characterizing invasive breast cancer cells by epigenetic characteristics – a method that involves analysing how particular regulatory proteins interact with DNA to control their expression – as well as by how the genes are amplified or abnormally expressed. The researchers reported that they used this technique to identify potential new prognostic markers to predict distinct clinical outcomes for two major subtypes of breast cancer.

“This paper describes a ground-breaking multi-omics technology to discover drivers of proliferative and invasive breast tumours,” said Xian Chen, PhD, professor in the UNC School of Medicine Department of Biochemistry & Biophysics. “We think that eventually, these tools could help doctors better predict which particular patients have a good response, or acquire resistance to treatment.” Doctors often rely on information about tumour size, whether the cancer has spread and the tumour subtype to make treatment decisions. In addition to clinical subtypes of breast cancer, researchers have discovered molecular subtypes that have been used to help make treatment decisions. However, Chen argues that existing markers do not adequately distinguish breast cancer patient sub-populations with different clinical outcomes.

“Single ‘omics’ approaches, which rely on either genomics, transcriptomics, or proteomics alone, fail to dissect the heterogeneity that contributes to individual patients’ variability in terms of their rates of tumour growth, metastasis, or susceptibility to anti-cancer therapies,” he said. “Because biomarkers are not available to distinguish distinct patient sub-populations that are either responsive or resistant to particular drugs, doctors do not have all the tools they need to predict patient response to treatment and outcomes.”
In their study, the researchers wanted to see if they could stratify patients beyond existing molecular subtypes. Their goal was to develop a method to determine which patients within a single subtype would develop resistance or invasive cancer. There are five major molecular subtypes of breast cancer, which are classified based on how genes are expressed in a tumour.

Chen and his colleagues analysed luminal breast cancer and basal-like breast cancer, which is more commonly known as triple negative breast cancer, using breast cancer samples from two large international studies, The Cancer Genome Atlas and the Molecular Taxonomy of Breast Cancer International Consortium.

To move beyond subtype for identifying exactly which patients might develop resistance, they first sorted the most invasive tumour cells in frozen tissue using a molecular probe that was able to distinguish tumour from adjacent non-malignant cells or tissue by binding to an epigenetic regulator, or a histone methylase, called G9a. This enzyme has been reported by other scientists to be abnormally upregulated in many cancer types, including breast cancer.

They then identified select proteins that were working with G9a as partners-in-crime, and worked backwards from there to identify the genetic abnormalities linked to those partner proteins in the cancer cell. They found in many instances the genes for these interactor proteins were amplified in multiple copies, or abnormally overexpressed, rather than mutated.

“Nowadays, people think somatic mutations of select genes are the primary drivers of tumorigenesis,” Chen said. “We didn’t see many mutations on our identified driver genes. We actually found the genes encoding those interactors have a high frequency amplification in breast cancer patients with poor prognosis.”

They then used this information to generate sets of genes that encoded these “interactor proteins,” and identified those linked to poor prognosis in patients. Looking ahead, Chen and his colleagues plan to determine the specificity and sensitivity of multi-omic aberrations of particular interactor gene sets as new systems biomarkers to predict cancer patient prognosis.

University of Northern Carolina

www.med.unc.edu/biochem/news/

New findings could improve diagnosis, treatment of depression

Researchers at the University of California, Berkeley, have identified biomarkers – genes and specific brain circuits in mice – associated with a common symptom of depression: lack of motivation.

The finding could guide research to find new ways to diagnose and potentially treat individuals suffering from lack of motivation and bring closer the day of precision medicine for psychiatric disorders like depression.
Depression is the most prevalent mental health disorder in the world, affecting around 9% of the American population each year, and is among the top causes of disability in the workplace. Depression symptoms can differ significantly between patients who have the same depression diagnosis, and the lack of a connection between symptoms and treatments is a main reason that about half of all people with depression fail to respond to medication or other therapies, and that side effects of these medications are common.

“If we had a biomarker for specific symptoms of depression, we simply could do a blood test or image the brain and then identify the appropriate medication for that patient,” said Stephan Lammel, a UC Berkeley assistant professor of molecular and cell biology. “That would be the ideal case, but we are far away from that situation right now.”

Now, for the first time, Lammel and his team have identified genes in a brain region – the lateral habenula – that are strongly turned on, or upregulated, in mice that show reduced motivation as a result of chronic stress. This brain region in mice is not associated with other depression symptoms, including anxiety and anhedonia, the inability to feel pleasure.

“We think that our study not only has the potential to transform how basic scientists study depression in animals, but the combination of anatomical, physiological and molecular biomarkers described could lay the foundation for guiding the development of the next generation of antidepressants that are tailored to specific depression symptoms,” Lammel said.

Lammel is senior author of a paper describing the discovery that appears this week in the journal Neuron. The study was led by first author Ignas Cerniauskas, who is a UC Berkeley graduate student.

Lammel and Cerniauskas work on mouse models of depression that have been a mainstay of basic research on this disorder for the past 60 years. Putting mice under constant stress produces at least three common symptoms of human depression – anxiety, lack of motivation and loss of pleasure – that scientists study to try to understand the disorder in humans.

Until now, however, researchers have sought answers by disregarding the variability of symptoms and instead categorizing all mice as either stressed (“depressed”) or non-stressed (“not depressed”). Cerniauskas and Lammel wanted to try to find changes in the brain that were associated with each specific symptom.

“Unfortunately, depression treatment is currently often based on guesswork. No one treatment works for everyone, and no one has objective data on how to differentiate the enormous variability of depression symptoms and subtypes,” Lammel said. “If we understand specifically how the brain changes in those animals with one certain type of symptom, there may be a way we can specifically reverse these symptoms.”

In response to a recent small clinical study in which doctors electrically stimulated the lateral habenula and found symptom improvement in depressed patients who were resistant to other therapies, Lammel and Cerniauskas decided to investigate that area of the brain. The lateral habenula has received increasing attention in the last few years, in part because it is connected to the dopamine and serotonin systems in the brain, both of which are known to be involved in depression. The most common drugs currently used to treat depression are serotonin reuptake inhibitors (SRIs) such as Zoloft and Prozac.

“After chronic stress, there is an increase in the neural activity of the lateral habenula cells – they fire more, they become overactive – and we found that this overactivity was present only in mice that showed very strong deficits in motivated behaviour, but not in animals that showed anxiety or animals that showed anhedonia,” Lammel said.

His team subsequently identified the specific synapses, cells and circuits in the lateral habenula that are altered by chronic stress in these particular mice, and in collaboration with Csaba Földy and colleagues at the University of Zürich, they found genes that are overexpressed as well.

University of California – Berkley news.berkeley.edu/2019/10/28/new-findings-could-improve-diagnosis-treatment-of-depression/