Malaria is a leading cause of death for children living in Sub-Saharan Africa. Many children in rural areas seek care at local community health clinics, but these clinics lack reliable tests to distinguish severe and uncomplicated malaria. Working at a health centre in rural Uganda, researchers from the University of North Carolina at Chapel Hill demonstrated for the first time the potential of using a low-cost, routinely available rapid diagnostic test to detect severe malaria in children.
 “In many areas of rural areas of sub-Saharan Africa, malaria is inevitable. Children will be infected,” said Ross Boyce, M.D., MS.c., study author and a fellow in the UNC Division of Infectious Diseases. “Ensuring that those with the most severe form of the disease are quickly identified and treated, even when hours from the nearest hospital, is critically important to reducing the number of deaths.”
Over a period of six months, a total of 2,678 children with fever underwent testing for malaria using a rapid diagnostic test at the Bugoye Level III Health Center in the Kasese District of Western Uganda. Nearly half tested positive for malaria and 83 satisfied criteria for severe malaria. The sensitivity and specificity of the rapid diagnostic test for detecting severe malaria was 97.6 percent. The test was especially sensitive for children less than 5 years of age. Knowing when a child is suffering from severe malaria allows for a referral to a health centre better equipped to handle the disease’s grave manifestations.
“Rapid diagnostic tests have been around for awhile, and are generally considered standard of care in most malaria-endemic settings,” said Boyce. “However, what we’ve done is show that these relatively simple tests can be used in new ways to provide important information beyond just a positive or negative result. While it’s not perfect, the approach could help first-line healthcare workers – many of who have no formal medical training – make potentially lifesaving triage decisions.”
Boyce said further work is needed to validate and operationalize diagnostic and treatment algorithms so as not to overwhelm fragile referral networks.

University of North Carolina
globalhealth.unc.edu/2017/08/rapid-diagnostic-test-malaria/

Using fragments of circulating tumour DNA in blood, University of California San Diego School of Medicine researchers were able to identify theoretically targetable genetic alterations in 66 percent of patients with cancer of unknown primary (CUP), a rare disease with seven to 12 cases per 100,000 people each year.
In order to plan treatment for cancer in general, physicians first attempt to pinpoint the primary cancer — where the tumour first developed. In CUP, despite its spread throughout the body, the origin remains unknown, making treatment more difficult. The current standard of care is platinum-based combination chemotherapies with a median survival time of six to eight months.
In a study, researchers report that by sequencing circulating tumour DNA (ctDNA) derived from blood samples in 442 patients with CUP, they were able to identify at least one genetic alteration linked to cancer in 290 — 66 percent — of patients. Researchers used a screening test developed by Guardant Health that evaluates up to 70 genes. Based on known carcinogenic mutations, 99.7 percent of the 290 patients who had detectable tumour DNA in their bloodstream had genomic alterations that could hypothetically be targeted using existing FDA-approved drugs (as off-label use) or with therapies currently under investigation in clinical trials.
“By definition, CUP does not have a definite anatomical diagnosis, but we believe genomics is the diagnosis,” said Razelle Kurzrock, MD, director of the Center for Personalized Cancer Therapy at Moores Cancer Center at UC San Diego Health and senior author. “Cancer is not simple and CUP makes finding the right therapy even more difficult. There are multiple genes and abnormalities involved in different areas of the body. Our research is the first to show that evaluating circulating tumour DNA from a tube of blood is possible in patients with CUP and that most patients harbour unique and targetable alterations.”
“Another advantage of the liquid biopsy is that the location of the cancer does not matter,” said Shumei Kato, MD, assistant professor of medicine at UC San Diego School of Medicine and first author. “With a blood sample, we can analyse the DNA of tumours throughout the body to find targetable alterations. With tissue biopsies, we can only see genomic changes that are in that one site and that may not be the same as what is in different sites not biopsied, such as the lung or bone.”
Moores Cancer Centerhttp://tinyurl.com/y9lffvh3

In this age of fast fashion and fast food, people want things immediately. The same holds true when they get sick and want to know what’s wrong. But performing rapid, accurate diagnostics on a serum sample without complex and time-consuming manipulations is a tall order. Now, a team reports that they have developed a biosensor that overcomes these issues.
Field-effect transistor (FET)-based biosensors are ideal for point-of-care diagnostics because they are inexpensive, portable, sensitive and selective. They also provide results quickly and can be mass-produced to meet market demand. These sensors detect the change in an electric field that results from a target compound, such as a protein or DNA, binding to it. But serum has a high ionic strength, or a high concentration of charged ions, that can mask the targets. Previous research has reported use of pre-treatment steps, complex devices, and receptors with different lengths and orientations on the sensor surface, but with limited success. Alexey Tarasov and colleagues wanted to develop a new approach that would make it easier for FETs to be made as point-of-care diagnostic devices for serum analyses.
The researchers developed a FET sensor that included antibody fragments and polyethylene glycol molecules on a gold surface, which they linked to a commercially available transducer. In this configuration, different sensor chips can be swapped out for use with the same transducer. As a proof-of-principle, they tested the sensor with human thyroid-stimulating hormone. The team found that they could detect the hormone at sub-picomolar concentrations, well below the detection limit previously reported with FETs, when testing it at elevated temperatures. They say that the device could be modified to diagnose many conditions and illnesses, and is inexpensive and easy to use.
American Chemical Society http://tinyurl.com/y99pwak6

Researchers at the University of Pittsburgh have uncovered the mechanism by which neurons keep up with the demands of repeatedly sending signals to other neurons. The new findings, made in fruit flies and mice, challenge the existing dogma about how neurons that release the chemical signal dopamine communicate, and may have important implications for many dopamine-related diseases, including schizophrenia, Parkinson’s disease and addiction.
Neurons communicate with one another by releasing chemicals called neurotransmitters, such as dopamine and glutamate, into the small space between two neurons that is known as a synapse. Inside neurons, neurotransmitters awaiting release are housed in small sacs called synaptic vesicles.
“Our findings demonstrate, for the first time, that neurons can change how much dopamine they release as a function of their overall activity. When this mechanism doesn’t work properly, it could lead to profound effects on health,” explained the study’s senior author Zachary Freyberg, M.D., Ph.D., who recently joined Pitt as an assistant professor of psychiatry and cell biology. Freyberg initiated the research while at Columbia University.
When the researchers triggered the dopamine neurons to fire, the neurons’ vesicles began to release dopamine as expected. But then the team noticed something surprising: additional content was loaded into the vesicles before they had the opportunity to empty. Subsequent experiments showed that this activity-induced vesicle loading was due to an increase in acidity levels inside the vesicles.
“Our findings were completely unexpected,” said Freyberg. “They contradict the existing dogma that a finite amount of chemical signal is loaded into a vesicle at any given time, and that vesicle acidity is fixed.”
The team then demonstrated that the increase in acidity was driven by a transport channel in the cell’s surface, which allowed an influx of negatively charged glutamate ions to enter the neuron, thus increasing its acidity. Genetically removing the transporter in fruit flies and mice made the animals less responsive to amphetamine, a drug that exerts its effect by stimulating dopamine release from neurons.
“In this case, glutamate is not acting as a neurotransmitter. Instead it is functioning primarily as a source of negative charge, which is being used by these vesicles in a really clever way to manipulate vesicle acidity and therefore change their dopamine content,” Freyberg said. “This calls into question the whole textbook model of vesicles as having fixed amounts of single neurotransmitters. It appears that these vesicles contain both dopamine and glutamate, and dynamically modify their content to match the conditions of the cell as needed.”
In the future, the team plans to look more closely at how increases in vesicle acidification affect health. A number of brain diseases are characterized by abnormal dopamine neuron signalling and altered levels of the neurotransmitter.
“Since we have demonstrated that the balance between glutamate and dopamine is important for controlling the amount of dopamine that a neuron releases, it stands to reason that an imbalance between the two neurotransmitters could be contributing to symptoms in these diseases,” said Freyberg.
University of Pittsburghhttp://tinyurl.com/y7laad5d

ClearLLab reagents are the first to receive Food and Drug Administration (FDA) clearance (via the De Novo Process) to market them in the US.  They deliver the first preformulated, IVD antibody cocktails for leukemia and lymphoma immunophenotyping in the clinical lab. For clinical laboratories it means they no longer have to develop their own laboratory developed test (LDT), a technically demanding, manual, time-consuming, and potentially error-prone process. Previously, labs would have had to make and validate their own antibody cocktails.  ClearLLab reagents simplify and standardize the process.
 ‘FDA allows marketing of test to aid in the detection of certain leukemias and lymphomas’ with the FDA confirming that the test ‘provides consistent results to aid in the diagnoses of these serious cancers’.  The FDA evaluated data from a multi-site clinical study which compared panel results to alternative detection methods.
Dr Mario Koksch, Vice President and General Manager of Beckman Coulter’s Cytometry Business Unit said: “Flow cytometry is a powerful tool for the detailed and fast analysis of complex populations, with the technique becoming increasingly valuable to the clinical hematology laboratory. “Clearance to market the first IVD L&L reagents in the US has opened the door to the expansion globally of our clinical reagent and instrument portfolio.”  
ClearLLab reagents deliver fast and accurate qualitative identification of various hematolymphoid cell populations by immunophenotyping on the FC500 flow cytometer.  With the reliability of a standardized kit and protocols, the preformulated combinations offer LEAN-focused benefits which reduce manual preparation and validation time, accelerate sample preparation time, improve workflow, streamline lab inventory management and provide confidence in the accuracy and reliability of results.
As Dr Koksch added: “The routine use of ready-to-use ClearLLab reagents delivers greater efficiency and cost savings.  Preformulated antibody combinations enable the lab to avoid the potential errors of manual antibody cocktail preparation, with the reassurance of standardized reporting to international guidelines.”
ClearLLab reagents follow the 2006 Bethesda International Consensus Recommendations on the Flow Cytometric Immunophenotypic Analysis of Hematolymphoid Neoplasia. They are compatible with the World Health Organization (WHO) 2016-revised classification of myeloid neoplasms and acute leukemia.  WHO, in collaboration with the European Association for Hematopathology and the Society for Hematopathology, recently made important changes to the classification of these diseases. These included new criteria for the recognition of some previously described neoplasms as well as clarification and refinement of the defining criteria for others. www.beckman.com