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Archive for category: E-News

E-News

Hair testing shows high prevalence of new psychoactive substance use

, 26 August 2020/in E-News /by 3wmedia

Over a fourth of the eighty samples tested positive for new psychoactive substances.
In the last decade hundreds of new psychoactive substances (NPS) have emerged in the drug market, taking advantage of the delay occurring between their introduction into the market and their legal ban.  According to the Drug Enforcement Agency (DEA) NPS describes a recently emerged drug that may pose a public health threat.  The DEA issues a quarterly Emerging Threat Report, which catalogues the newest identified NPS.
NPS tend to mimic the psychotropic effects of traditional drugs of abuse, but their acute and chronic toxicity, and side-effects are largely unknown.  While seizure data from the DEA is often used to indicate what new drugs are being sold in the US, there is a lack of research examining and confirming who has been using such drugs.
Joseph J. Palamar, PhD, MPH, a New York University researcher, has been researching incidental and intentional use of NPS by young adults.  His current line of inquiry has focused on survey methods, qualitative interviews, and hair sampling to ascertain frequency and type of NPS use by nightclub-goers–a demographic which traditionally has a relaxed view towards recreational drug experimentation and use.
NPS are common adulterants in drugs such as ecstasy (MDMA), which has seen an increase in popularity since it became marketed as “Molly”.  Ironically, “Molly” connotes a product that is pure MDMA. In a related study, Palamar and his team found that four out of ten nightclub/festival attendees who used ecstasy or “Molly” tested positive for “bath salts” despite reporting no use.
In their current study, “Hair Testing for Drugs of Abuse and New Psychoactive Substances in a High-Risk Population,” Dr. Alberto Salomone, an affiliated researcher at the Centro Regionale Antidoping e di Tossicologia “A. Bertinaria”, Orbassano, Turin, Italy and Dr. Palamar, affiliated with NYU’s Center for Drug Use and HIV Research (CDUHR), collected hair samples from 80 young adults outside of New York City nightclubs and dance festivals, from July through September of 2015.  Hair samples from high-risk nightclub and dance music attendees were tested for 82 drugs and metabolites (including NPS) using ultra-high performance liquid chromatography–tandem mass spectrometry.
“Hair analysis represents a reliable and well-established means of clinical and forensic investigations to evaluate drug exposure, said Dr. Salomone.  “Hair is the most helpful specimen when either long-time retrospective information on drug consumption is of interest.” “Most NPS can no longer be detected in urine, blood, or saliva within hours or days after consumption, but hair is particularly beneficial because many drugs can be detected months after use.”
Of the eighty samples, twenty-six tested positive for at least one NPS—the most common being a “bath salt” (synthetic cathinone) called butylone (present in twenty-five samples). The “bath salts” methylone and even alpha-PVP (a.k.a.: “Flakka”) were also detected. The researchers find the presence of Flakka alarming as this drug has been associated with many episodes of erratic behaviour and even death in Florida. Other new drugs detected included new stimulants called 4-FA and 5/6-APB.
“We found that many people in the nightclub and festival scene have been using new drugs and our previous research has found that many of these people have been using unknowingly,” said Dr. Palamar, also an assistant professor of Population Health at NYU Langone Medical Center (NYULMC).
Hair analysis proved a powerful tool to Drs. Salomone and Palamar and their team, allowing them to gain objective biological drug-prevalence information, free from possible biases of unintentional or unknown intake and untruthful reporting of use.

NYU Langone Medical Center
www.nyu.edu/about/news-publications/news/2017/march/hair-testing-shows-high-prevalence-of-new-psychoactive-substance.html

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Researchers study patients’ genetic and susceptibility risk factors in hopes of finding the path to cure lymphedema

, 26 August 2020/in E-News /by 3wmedia

Each year, about 1.38 million women worldwide are diagnosed with breast cancer. Advances in diagnosis and treatment have facilitated a 90-percent, five-year survival rate, among those treated. However, with the increased rate and length of survival following breast cancer, patients face a lifetime risk of developing lymphedema, one of the most distressing and feared late onset breast cancer-related effects.

Lymphedema is an abnormal accumulation of lymph fluid in the ipsilateral body area, or upper limb. This remains an on-going major health problem affecting more than 40 percent of 3.1 million breast cancer survivors in the U.S. Lymphedema following breast cancer surgery is typically considered to be primarily due to the mechanical injury from surgery. However, recent research has found that inflammation-infection and higher body mass index are also main predictors of lymphedema.

Researchers from New York University Rory Meyers College of Nursing (NYU Meyers), led by Dr. Mei R. Fu, PhD, RN, FAAN, conducted a study, “Precision assessment of heterogeneity of lymphedema phenotype, genotypes and risk prediction,” to address this phenomenon and prospectively examine phenotype of arm lymphedema by limb volume and lymphedema symptoms in relation to inflammatory genes in women treated for breast cancer.

The study is the first of its kind in exploring associations between genetic susceptibility targeting identified phenotypic risk factors of inflammation and heterogeneous phenotypes of lymphedema.

“It remains puzzling that up to 23% of survivors who only had lumpectomy with sentinel lymph node biopsy of 1 or 2 lymph nodes removed have developed lymphedema, while some survivors who had mastectomy with more than 10 lymph nodes removed have not,” said Dr. Fu. “There is a critical need to understand heterogeneity of lymphedema phenotype in relation to assessment of lymphedema phenotype and related biological mechanism.”

The study consisted of 136 women with a mean age of 52 with a first time diagnosis of breast cancer (Stage I-III), and were scheduled for surgical treatment of lumpectomy or mastectomy. The researchers measured data at 4-8 weeks post-surgery and 12 months post-surgery to monitor development of lymphedema during this period. They used lymphedema phenotyping to measure more symptoms than the typical method of observing swelling and limb volume. The symptom phenotyping was important in indicating early stage lymphedema where limb volume cannot be assessed yet.

The researchers found that using symptom phenotyping, prior to surgery, only one participant had more than 8 symptoms and only 18 had 1-7 symptoms. At 4-8 weeks post-surgery all participants had at least one symptom, 53% had 1-7 symptoms, and 46% had more than 8 symptoms, whereas only 16% had arm lymphedema defined by limb volume increase. At 12 months post-surgery 26.5% had more than 8 symptoms and 63% reported 1-7 symptoms, whereas only 22.8% had arm lymphedema as defined by limb volume.
Additionally, prior to surgery, identification of symptom phenotypes was not feasible, as 86% of participants were symptom-free. However, at 4-8 weeks post-surgery 58.1% of participants were classified as the phenotype of impaired limb mobility, with 86% discomfort, and 55.9% fluid accumulation. At 12 months 55.2% of participants were classified as the phenotype of impaired limb mobility with 38.2% pain/discomfort, and 44.1% fluid accumulation.

This data found significant associations between genotypes related to several lymphatic and inflammatory genes and symptom phenotypes of impaired limb mobility, fluid accumulation, and pain/discomfort. The data further provides support for heterogeneity of lymphedema phenotypes, especially phenotype of symptom clusters based on biological mechanisms.

Dr. Fu notes that the sample size and only 12-month period of observation does put limitations on the study.

New York Universitywww.nyu.edu/about/news-publications/news/2017/february/nyu-researchers-study-patients-genetic-and-susceptibility-risk-f.html

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A biomarker for cancer of the oropharynx

, 26 August 2020/in E-News /by 3wmedia

Cancer of the oropharynx has become increasingly common: In the United States alone, the number of newly diagnosed cases has tripled over the past three decades. About 70 percent of these tumours are caused by infection with human papillomavirus (HPV) type 16.

Tim Waterboer and his colleagues at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) in Heidelberg have now revealed that an antibody test that they developed can detect early if a person has a very high risk of developing an HPV-associated cancer of the oropharynx. The DKFZ researchers collaborated in this project with colleagues from the International Agency for Research on Cancer (IARC) and the U.S. National Cancer Institute.

The immune system responds to an infection with HPV by producing antibodies against components of the virus. HPV protein E6 is produced by chronically infected cells and plays an important role in the development of cancer. Therefore, antibodies against E6 are regarded as very valuable indicators.

In the new study, the scientists investigated blood samples from the U.S. PLCO study. For this early cancer detection study, approximately 150 000 healthy participants were recruited between 1993 and 2001 and cancers that they developed in the period under investigation were documented. The DKFZ researchers studied 198 blood samples from patients with tumours of the oropharynx. The samples had been taken when the participants entered the study, i.e., long before the onset of the disease. The control samples were from 924 PLCO participants without cancer diagnosis.

In 42.3 percent of the patients with oropharyngeal cancer, the DKFZ researchers were able to detect antibodies against HPV16 E6 in their blood samples. "This pretty much corresponds to the percentage of HPV-related cases of oropharyngeal cancer that we expected to find for that time in the American population," Tim Waterboer said. By comparison, only 0.5 percent of individuals in the control group tested positive to HPV16 E6.

Tumour tissue of some study patients was also available for study besides the blood samples. Based on the activity of viral genes in the tissue, the researchers were able to identify the tumours that had been caused by HPV. They found that only those patients tested positive to the antibodies whose cancer was in fact associated with HPV16.

If the test result for HPV16 E6 antibodies is positive once, it remains stable over many years, discovered the researchers in study participants from whom blood samples had been obtained repeatedly over a long time. In some cases, the blood samples had been taken up to 13 years prior to cancer diagnosis. "This means that a single blood sample test taken at any point of time might be sufficient for assessing a person’s risk for developing cancer of the oropharynx within the next 10 years," said Waterboer.

Nevertheless, detection of HPV16-E6 antibodies is –at least for now – not a suitable method for early cancer detection in larger population groups. "The occurrence of new cases of oropharyngeal cancer is rather low at about five cases per 100 000 inhabitants," said Waterboer, who is the study head. "That means that although the test is highly specific, very many healthy people would receive false positive results. However, in certain high-risk groups, up to ten times more people can develop the disease. HPV16 E6 antibody detection is the first ever easy-to-analyze biomarker that enables us to narrow down the circle of individuals who are at an extremely high risk of developing the cancer." The DKFZ virologists are currently examining possibilities of making the biomarker applicable in the clinic.

However, the test for antibodies against HPV16 E6 is not suitable for assessing the risk for cervical cancer and other HPV-associated cancers in genital areas. As opposed to cancer of the oropharynx, the revealing antibodies do not occur here before the cancer becomes clinically detectable.

DKFZwww.dkfz.de/en/presse/pressemitteilungen/2017/dkfz-pm-17-19-A-biomarker-for-cancer-of-the-oropharynx.php

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Scientists develop diagnostic tool for Familial Mediterranean Fever

, 26 August 2020/in E-News /by 3wmedia
Researchers at VIB and Ghent University have developed a tool to diagnose Familial Mediterranean Fever (FMF). Particularly common among Mediterranean populations, this genetic disease is characterized by inflammation, fever and severe pain. Because of its complex diagnosis, patients often remain untreated for many years, which can eventually lead to kidney failure. In collaboration with Ghent University Hospital and Antwerp University Hospital, VIB and Ghent University are now planning clinical trials  to further validate immunodiagnosis of FMF. 
In the Mediterranean basin, including the Middle East and Caucasus, FMF has a prevalence between 1 and 2 per 1,000 inhabitants. FMF is usually diagnosed during childhood, after which a daily, lifelong treatment is necessary. However, accurate diagnosis is complicated by a number of factors: other auto-inflammatory diseases show similar symptoms, the clinical picture is often incomplete in young children, atypical signs may occur, and a suggestive family history is sometimes lacking. Wrong or late diagnosis often even leads to unnecessary surgery and, ultimately, kidney failure.
The lab of professor Mohamed Lamkanfi (VIB-Ghent University) developed an alternative for today’s inadequate diagnosis, efficiently segregating FMF patients from people suffering from other auto-inflammatory diseases and healthy individuals. The tool detects changes in the body’s immune reaction to pyrin, a protein that is usually mutated in FMF. Following successful tests on mice, the tool has been validated in 13 patients in collaboration with physicians from Belgium and Italy. 
Prof. Mohamed Lamkanfi (VIB-Ghent University): “As next steps, we are setting up clinical trials in Belgium for which we are actively seeking volunteers – both FMF patients and people suffering from related inflammatory disorders. These trials are funded by, among other parties, the European Research Council and FWO (Research Foundation – Flanders). In addition, labs from the Netherlands and Italy have already expressed interest. We are also exploring possible collaborations with industrial partners in order to make our method available as a diagnostic kit.”
VIB
http://tinyurl.com/zpa6s88
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Can genetic testing determine antimicrobial susceptibility? EUCAST experts say not yet…

, 26 August 2020/in E-News /by 3wmedia

Experts at the European Committee on Antimicrobial Susceptibility Testing (EUCAST), who define the optimal drug concentrations to inhibit the growth of pathogens, have found that genetic methods cannot yet be used to test for susceptibility in a number of important bacterial species. Although there have been advances in whole genome sequencing (WGS), which allows to determine the DNA sequence of an organism’s genome at a single time, there are still several hurdles to overcome before this type of genetic testing can be used in clinical laboratories, they concluded.
A EUCAST subcommittee dedicated to reviewing the role of WGS in antimicrobial susceptibility testing (AST) considered the most recent published evidence on the use of whole genome sequencing as a tool for susceptibility testing. The group – comprising of over a dozen leading experts and led by Prof. Neil Woodford, Head of Public Health England’s Antimicrobial Resistance and Healthcare Associated Infections Reference Unit – did not rule out that it will one day be possible for a single assay to predict how a species of bacteria will respond to a specific antimicrobial drug, but there is little evidence to suggest we will reach this point in the near future.
EUCAST’s technical data coordinator, Prof. Gunnar Kahlmeter of the Central Hospital, Växjö, Sweden, said that it is premature to suggest that breakpoints and recommendations for phenotypic susceptibility testing will no longer be required as genetic methods will supersede them any time soon. “To be of use in a clinical situation, WGS will need to predict antimicrobial resistance and also antimicrobial susceptibility, which are two quite different things. It will also be necessary for WGS to quantify the degree of resistance for an organism, something which is currently not possible.”
The group has chosen to compare how WGS can predict whether or not the organism belongs to the wild type (is without resistance mechanisms) with the same prediction performed through the use of the epidemiological cut-off values (ECOFFs) developed by EUCAST. Whether or not and in that case how this can be extended to clinical breakpoints is discussed in the paper.
The EUCAST subcommittee also highlighted that there is currently no way to assess how accurate different WGS laboratories are, and that there is an urgent need to establish a single public database of all known resistance genes within different bacterial species so that data can be shared and compared more easily.
The EUCAST experts also note that WGS technology is currently limited because it cannot be used to analyse specimens directly – bacteria can only be sequenced once they have been cultured. This inevitably leads to significant time delays and additional financial costs, which is usually prohibitive for most laboratories.
EUCAST recommends that whole-genome sequencing should be made a research and funding priority in the future to expand on our current knowledge and to develop more sophisticated prediction tools. As bacteria continue to develop multiple resistance mechanisms, unravelling the genetics of their interaction with antimicrobials will become even more challenging and even more necessary, particularly as we face the spectre of extreme drug resistance and global failure of some antimicrobials.www.escmid.org

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20 Times Faster Biosensor

, 26 August 2020/in E-News /by 3wmedia

DGIST research team led by Professor CheolGi Kim has developed a biosensor platform which has 20 times faster detection capability than the existing biosensors using magnetic patterns resembling a spider web.
The sensing capability of a biosensor is determined by the resolution of the sensor and the movement and reaction rate of molecules. Many research groups in Korea and other countries have been improving the resolution through the development of nanomaterials but there has been a limitation to improve the sensors’ sensitivity due to the low diffusion transport of biomolecules toward the sensing region.                                
Professor Kim and his research team used a magnetic field in order to overcome the drawback that the movement of biomolecules such as proteins and DNA is slow when the transport only depends on diffusion. The biomolecules labelled with superparamagnetic particles and the use of an external magnetic field enabled the movement of the biomolecules to be easily controlled and detected with an ultra-sensitive magnetic sensor.
The research team developed a new biosensor platform using a spider web-shaped micro-magnetic pattern. It improved the sensing ability of the biosensor as it increased the ability to collect low-density biomolecules by attracting biomolecules labelled with the superparamagnetic particles to the sensing area.
The first author Byeonghwa Lim at DGIST’s Ph.D program of Emerging Materials Science elaborated on the biosensor platform, "We placed a spider web-shaped micro-magnetic pattern which was designed to move the superparamagnetic particles toward the center of the biosensor and a high sensitivity biosensor on the platform. When a rotating magnetic field is applied to a spider web-shaped magnetic pattern, it can attract biomolecules labelled with superparamagnetic particles faster to the sensor. The speed of the movement is very fast and it can detect the subject 20 times faster than the diffusion method."
The research team also succeeded in monitoring the biomolecules conjugated to the superparamagnetic particles at a distance from the sensing area by utilizing the biosensor platform. In addition, the team has identified that the superparamagnetic particles not only play the role of biomolecular cargo for transportation, but also act as labels for the sensor to indicate the location of biomolecules.
Professor Kim stated "The existing biosensors require long time to detect low density biomolecules and result in poor sensing efficiency as they only depend on diffusion. The magnetic field based biosensor platform improves the collection capability of biomolecules and increases the speed and sensitivity of the biomolecules movement. Therefore, we are planning to use this platform for early diagnosis as well as recurrence diagnosis of diseases such as cancer. "

DGIST
en.dgist.ac.kr/site/dgist_eng/menu/508.do?siteId=dgist_eng&snapshotId=3&pageId=429&cmd=read&contentNo=34358

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Sorting out risk genes for brain development disorders

, 26 August 2020/in E-News /by 3wmedia

Gene discovery research is uncovering new information about similarities and differences underlying various neurodevelopmental disorders.  These are a wide-ranging collection of conditions that affect the brain.  They include autism, intellectual impairments, developmental delays, attention deficits, tic disorders and language difficulties.

To better understand how gene-disrupting mutations contribute to the biology of neurodevelopmental disorders, researchers recently conducted a large, international, multi-institutional study.   

More than 11,700 affected individuals and nearly 2,800 control subjects underwent targeted DNA sequencing of 208 suspected disease-risk genes. The candidate genes were chosen based on previously published studies.  By looking at greater numbers of cases and using a reliable yet inexpensive molecular inversion probe, the project team wanted to measure the statistical significance of individual, implicated genes.

The study leaders were Holly A. F. Stessman, Bo Xiong and Bradley P. Coe, of the genome sciences laboratory of Evan Eichler at the University of Washington School of Medicine and the Howard Hughes Medical Institute.  Stessman is now at Creighton University.

Their samples were collected through the Autism Spectrum/Intellectual Disability 15-center network spanning seven countries and four continents.  An advantage of this collection, the researchers said, is the ability to check back on a large fraction of cases to try to relate genetic results to clinical findings.  

In their study population, the researchers associated 91 genes with the risk of a neurodevelopmental disorder. These included 38 genes not previously suspected of playing a role.  Based on some of the family studies, however, mutations even in two or more of the risk genes may not be necessary or sufficient to cause disease.

Of the 91 genes, 25 were linked with forms of autism without intellectual disability. The scientists also described a gene network that appeared to be related to high-functioning autism.  Individuals with this form of autism have average to above average intelligence, but may struggle in learning to talk, interact socially, or manage anxiety and sensory overload.  
While observing that some genes were more closely associated with autism and others with intellectual or developmental impairments, the researchers found that most of the genes implicated were mutated in both conditions.  This result reinforces the substantial overlap among these conditions in their underlying genetics and observable characteristics.

“Most of these genes are clearly risk factors for neurodevelopmental disorders in a broad sense,” the researchers explained.  “But analysis of both the genetic and subsequent patient follow-up data did single out some genes with a statistical bias towards autism spectrum disorder, rather than an intellectual disability or developmental delay.”

Additional findings suggest that less severe mutations may be behind autism that is not accompanied by intellectual disability.

University of Washington Health Systemhsnewsbeat.uw.edu/story/sorting-out-risk-genes-brain-development-disorders

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Aggressive form of leukemia linked to defective ‘protein factory’

, 26 August 2020/in E-News /by 3wmedia

Twenty to forty percent of the patients with the type of leukemia known as multiple myeloma have a defect in the ‘protein factory’ of the cell: the ribosome. These patients have a poorer prognosis than patients with intact ribosomes. At the same time, they respond better to a drug that already exists. These are the findings of a study by the KU Leuven Laboratory for Disease Mechanisms in Cancer, led by Professor Kim De Keersmaecker.
Multiple myeloma (MM, also known as Kahler’s disease) is a blood cancer whereby the plasma cells in the bone marrow start proliferating malignantly. MM cannot be cured and is most common among older people. Various treatments exist to temporarily suppress the disease, but the challenge is determining to which treatment the patient will respond best.
Doctoral student Isabel Hofman discovered defects in the ribosome of MM patients. “The ribosome is the protein factory of a cell. In MM patients, one part of the ribosome is produced less in 20 to 40 percent of the patients, depending on how aggressive the cancer is. We suspect that their cells are still producing protein, but that the balance is somewhat disrupted. In any case, we found that these people have a poorer prognosis than MM patients with an intact ribosome,” explains Professor De Keersmaecker.
One possible treatment for MM is the use of proteasome inhibitors. “The proteasome is the protein demolition machine in a cell. There’s a type of drugs, including Bortezomib, that inhibits its functioning. How the defects in the ribosome influence the proteasome is not quite clear yet. But we discovered that patients with a defective ribosome respond better to Bortezomib. In other words, their poorer prognosis can be offset by this treatment. On the basis of these findings, we can now develop tests to identify defects in the ribosome and thus determine which therapy will have most effect in a specific patient.”
The notion that cancer is related to ribosome defects is a relatively new concept in science. “A few years ago, we discovered defects in the ribosome of patients with acute lymphatic leukemia. Now we know that the same applies to MM. In all likelihood, this will also hold true for other types of cancer.

KU Leuven http://tinyurl.com/jnubnm7

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EUROIMMUN announces option agreement on Zika virus serology

, 26 August 2020/in E-News /by 3wmedia

EUROIMMUN and Roche announced early April 2017 that they have entered into an option agreement under which Roche gains access to intellectual property in the field of Zika virus immunodiagnostics assigned to EUROIMMUN.
In January 2016, EUROIMMUN became the first company in the world to launch antibody tests that are capable of indicating both an acute Zika virus infection (usually from the fifth day after the onset of symptoms) and previous episodes of the illness. The EUROIMMUN Anti-Zika Virus ELISA is also the first commercial serological Zika test to receive CE (Europe) and ANVISA (Brazil) Mark registrations.
Infectious diseases represent a major cause of death worldwide. Every year, 1.45 million people die of viral hepatitis and in 2014, 1.2 million died of AIDS-related causes. After the 2014 Ebola outbreak, Zika is the latest virus to create significant public health concern. There is growing body of evidence that links the Zika virus to birth defects in fetuses and newborns, and neurological complications in adults. Public health officials and experts in the field consider these associations valid based on a number of epidemiological studies, modelling, and use of predefined criteria. Concern among public health bodies is high since there are currently no effective interventions to control vector mosquitoes.
In order to prepare for the growing health emergency, EUROIMMUN launched the Anti-Zika Virus ELISA (IgM or IgG), a fully automated, highly specific test with reduced cross-reactivity to other flaviviruses. The Anti-Zika Virus ELISA (IgM or IgG) is based on a highly specific, recombinant non-structural viral protein (NS1), which avoids the cross reactivity typically associated with serological tests based on whole virus antigens. Data from panels of well-characterised sera have confirmed that there is no cross reactivity with flaviviruses including dengue, West Nile, yellow fever, tick-borne encephalitis and Japanese encephalitis viruses. In studies on clinically and serologically characterised samples the IgM and IgG ELISAs showed nearly 100% specificity. Furthermore, the combination of IgM and IgG ELISAs provides highest sensitivity of 97%. Serological testing provides a much longer window for diagnosis compared to direct detection methods. This type of testing helps assess a recent infection even when ribonucleic acid (RNA) is no longer detectable – if, for example, the infection is resolved or has moved into the chronic phase. It is therefore critical that any serology assay be extremely specific to Zika to reduce cross-reaction with these other viruses, thus avoiding a potential false positive that could lead to erroneous interpretation of a patient’s immune status.
“Until now it has been virtually impossible to distinguish a Zika virus infection by antibody testing from infections with other flaviviruses like dengue or West Nile virus,” said Dr. Wolfgang Schlumberger, Vice Chairman of the EUROIMMUN’s Board. “Our test may be used by travellers to areas with Zika virus outbreaks to assess any health risks and to take appropriate precautions upon return, and cooperating with Roche will help us make it available to the broadest possible spectrum of patients.”
Learn more about the Anti-Zika Virus ELISA.

 
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“Jumping gene” uncovers genetic networks involved in prostate and breast cancer

, 26 August 2020/in E-News /by 3wmedia

Mutations in tumour suppressor genes mean that they can no longer keep tumours from growing. In developing cancer, often several mutations come into play. Using "jumping genes," scientists from the Technical University of Munich (TUM) and the German Cancer Consortium (DKTK) together with teams from Great Britain and Spain have identified a number of genes that can influence the growth of prostate and breast tumours.
Prostate cancer is the most common cancer in men in Germany with around 63,000 patients diagnosed every year. About half of them have an altered Pten gene. This well-known tumour suppressor gene can help prevent cancer development in healthy people by inducing cell death in tumour cells. However, little is known about which other genes cooperate with Pten to prevent cancer. In order to find out more, the international team designed a new method. They converted the Pten-Gene in mice into a mobile DNA element known as a transposon. This transposon "jumps" from its original position and lands at a random position throughout the genome, damaging and thus deactivating genes into which it is inserted. The transposons "starting point", i.e. the Pten-Gene, is deactivated as well. In the experiment, cancers would grow when the transposon damaged a tumour suppressor gene that co-operated with Pten.
"Using the new transposon-based approach, we were able to systematically search the genome for genes cooperating with Pten and influencing the development of prostate cancer, but also other forms of cancer like breast or brain cancer," says Dr Juan Cadiñanos, joint lead author from the Instituto de Medicina Oncologica y Molecular de Asturias and the Wellcome Trust Sanger Institute in Britain. "This approach could also be used to look into relations between other genes."
The researchers analysed 278 prostate, breast and skin tumours and revealed hundreds of genes that could cooperate with Pten and act as further tumour suppressor genes. Human cell lines and data from human prostate tumours were then used to study the five most promising genes. "Coupled with Pten inactivation, a loss of function in these genes led to typical cancer pathways being activated," says Jorge de la Rosa, one of the study’s first authors. The researchers found that in human prostate tumours, the genes in question were considerably limited in their function.
Transposon-based approaches are useful for looking into the molecular basics of the development of tumours. "They allow us to find genes connected to cancer that are hard to find using other methods," says Roland Rad, a DKTK-Professor for translational Oncology at TUM’s Klinikum rechts der Isar. "In order to understand the biology of tumour development, we must uncover the complex tumor suppressor networks. This is a prerequisite for developing new therapeutic strategies."

DKFZ
www.dkfz.de/en/presse/pressemitteilungen/2017/dkfz-pm-17-14b-Jumping-gene-uncovers-genetic-networks-involved-in-prostate-and-breast-cancer.php

https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 0 0 3wmedia https://clinlabint.com/wp-content/uploads/sites/2/2020/06/clinlab-logo.png 3wmedia2020-08-26 09:33:002021-01-08 11:09:34“Jumping gene” uncovers genetic networks involved in prostate and breast cancer
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