Laboratory medicine is one of the major supporting areas of healthcare management. Though representing less than 2% of health expenditure, it affects over 70% of clinical decisions which are taken based on laboratory results and this trend is even growing in the last decade. One of the drivers of this increased significance is a better understanding of the different roles that proteins, enzymes, substrates and electrolytes playsin keeping the organism in healthy state, and how some imbalances in their normal levels could become predictors of future diseased states. This has led in the last few years to develop a number of highly specialized tests focused on uncommon parameters, often referred to as esoteric tests or special tests. Accounting for about 15% in the value of all tests performed in the field of biochemistry testing, but just 2% in the number of tests, they are one of the key drivers of the expansion in the market, as new and more useful tests are proposed. Nowadays, they grow at a rate close to 15% in comparison with the paltry 1% of routine tests and a new business model has appeared for the laboratory as referral centre for those tests, gathering requests from other laboratories more focused on routine tests and for which implementing special tests in their menu is not cost-effective. Biosystems, as a leading manufacturer of reagents and instruments world-wide is also actively expanding into this area with a number of reagents that have been clinically accepted as valuable markers or monitors of several disease states. The menu of test includes parameters for cardiac risk assessment like homocysteine, that is associated with an increased risk of myocardial infarction and venous thrombosis; urolithiasis recurrence management, with parameters like serum oxalate, associated with primary hyperoxaluria, or angiotensin converting enzyme, associated with sarcoidosis; the biochemical profile of fertility in seminal plasma, with parameters like zinc, associated with male infertility; or enzyme activity associated with some critical metabolic pathways relevant in emergency management, like aldolase (muscle weakness of several origins), beta-hydroxybutyrate (ketosis in diabetic patients) or lactate (lactic acidosis after a congestive heart failure). All of these tests are available for BioSystems’ automatic systems A15, A25 and BA400, but can also be adapted to many other common analysers in the market.

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While research has identified hundreds of genes required for normal memory formation, genes that suppress memory are of special interest because they offer insights into how the brain prioritizes and manages all of the information, including memories, that it takes in every day. These genes also provide clues for how scientists might develop new treatments for cognitive disorders such as Alzheimer’s disease.

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have identified a unique memory suppressor gene in the brain cells of Drosophila, the common fruit fly, a widely recognized substitute for human memory studies.

The study, which was led by Ron Davis, chair of TSRI’s Department of Neuroscience].

Davis and his colleagues screened approximately 3,500 Drosophila genes and identified several dozen new memory suppressor genes that the brain has to help filter information and store only important parts. One of these suppressor genes, in particular, caught their attention.

“When we knocked out this gene, the flies had a better memory—a nearly two-fold better memory,” said Davis. “The fact that this gene is active in the same pathway as several cognitive enhancers currently used for the treatment of Alzheimer’s disease suggests it could be a potential new therapeutic target.”

When the scientists disabled this gene, known as DmSLC22A, flies’ memory of smells (the most widely studied form of memory in this model) was enhanced—while overexpression of the gene inhibited that same memory function.

“Memory processes and the genes that make the brain proteins required for memory are evolutionarily conserved between mammals and fruit flies,” said Research Associate Ze Liu, co-first author of the study. “The majority of human cognitive disease-causing genes have the same functional genetic counterparts in flies.”

The gene in question belongs to a family of “plasma membrane transporters,” which produce proteins that move molecules, large and small, across cell walls. In the case of DmSLC22A, the new study indicates that the gene makes a protein involved in moving neurotransmitter molecules from the synaptic space between neurons back into the neurons. When DmSLC22A functions normally, the protein removes the neurotransmitter acetylcholine from the synapse, helping to terminate the synaptic signal. When the protein is missing, more acetylcholine persists in the synapse, making the synaptic signal stronger and more persistent, leading to enhanced memory. 

“DmSLC22A serves as a bottleneck in memory formation,” said Research Associate Yunchao Gai, the study’s other co-first author. “Considering the fact that plasma transporters are ideal pharmacological targets, drugs that inhibit this protein may provide a practical way to enhance memory in individuals with memory disorders.”

The next step, Davis added, is to develop a screen for inhibitors of this pathway that, independently or in concert with other treatments, may offer a more effective way to deal with the problems of memory loss due to Alzheimer’s and other neurodegenerative diseases. Scripps Florida

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

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

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