EKF Diagnostics, the global in vitro diagnostics company, has published a guide to ‘Diabetes and HbA1c testing’ which can be found at EKF’s new Diabetes Portal (www.ekfdiagnostics.com/diabetes-portal.html). This new educational guide draws on EKF’s expertise in the diagnosis and monitoring of diabetes and associated conditions. It provides an overview of the global diabetes ‘epidemic’, symptoms and complications, through to discussion on methods for diagnosis and monitoring using both glucose and HbA1c testing, with consideration given to factors influencing their measurement.
Diabetes is a growing issue, particularly in developing countries, with five million people dying from diabetes related complications in 2015 alone. Although not an ‘epidemic’ in the conventional sense, there are currently 415 million people living with diabetes and this is predicted to grow to 642 million by 2040. Approximately 46% of people living with diabetes are doing so without a full and proper diagnosis with subsequent complications, and associated healthcare costs.
There are multiple options for the diagnosis of diabetes, most of which involve measuring the level of glycemic control a person exhibits. In addition to methods such as fasting plasma glucose and two-hour plasma glucose, another option is to use glycated hemoglobin (HbA1c) which reflects average plasma glucose over an 8-12 week period. As well as lab-based testing, WHO has approved HbA1c for diabetes diagnosis with a Point of-Care-Testing (POCT) device, providing the test is undertaken by a trained professional adhering to an appropriate External Quality Assurance scheme and using a methodology traceable to the IFCC reference method. POCT HbA1c testing gives a strong indication of both diabetes and pre-diabetes within a timeframe that enables immediate intervention.
Since it is not impacted by the same issues as blood glucose monitoring, HbA1c testing is fast becoming the preferred technique for diabetes and pre-diabetes diagnosis and monitoring. There are situations where use of HbA1c is not appropriate though. EKF’s new Guide includes discussion on both glucose and HbA1c testing and where factors may influence measurement of both diagnostic markers.
“The often ‘low to no’ maintenance approach to disease management of diabetes is not only dangerous but can also significantly contribute to ongoing healthcare costs. At present, approximately 12% of global health expenditure is spent on diabetes, and without significant changes to the way patients and health systems monitor glycemic control this will surely rise,” said Gavin Jones, Global Product Manager for Diabetes Care at EKF Diagnostics. “To enhance patient outcomes and reduce the cost for long-term healthcare of the diabetic and pre-diabetic population, we aim to improve patient access to diabetes care techniques, whatever their location. This can be achieved by providing affordable, easy-to-use POCT analysers and chemistry assays for both diabetes diagnosis and monitoring.”
EKF’s expertise and product range cover all aspects of diabetes care, from research and hospital laboratories to diabetes clinics, emergency rooms and GP surgeries. Products include the Biosen C-Line glucose analyser, which uses chip sensor technology to provide low cost, fast and lab accurate glucose results. Quo-Test and Quo-Lab point-of-care HbA1c analysers that deliver results meeting NGSP and IFCC POC requirements in four minutes. And lastly, to aid the diagnosis and monitoring of diabetes related conditions such as ketoacidosis, EKF offers Beta-Hydroxybutyrate LiquiColor Reagent and the handheld STAT-Site M β-HB strip-based analyser.
www.ekfdiagnostics.com

Yale experts and their partners in a national research consortium have identified several genes and gene clusters associated with the immune response to influenza (“flu”) vaccination. The findings point to the prospect of using genetic profiles to predict individual responses to the flu vaccine.
The global impact of influenza is substantial, with seasonal epidemics estimated to result in 3-5 million cases of severe illness, and 250,000 to 500,000 deaths annually worldwide. Vaccination is the best way to protect against flu infection, but the composition of the seasonal vaccine changes from year to year. Moreover, effectiveness of the vaccine varies widely among individuals.
Previous studies, including a study done at Yale, have sought to identify changes in gene expression associated with successful flu vaccination but focused on relatively small numbers of participants. The new study included six different cohorts receiving the flu vaccine from across the country; research centres included Yale, the Baylor Research Institute, Emory University, the Mayo Clinic, and the National Institutes of Health. The size of the cohort — more than 500 individuals — allowed researchers to not only identify genes and gene clusters associated with vaccine response, but also confirm these findings in an independent cohort of participants.
Analysing the data, the research team identified several gene “signatures,” or groups of genes, that were associated with a stronger response to the flu vaccine. The response was determined by increases in antibodies that protect against infection.
We “were able to identify genes at baseline, before vaccination, that would predict how individuals would respond to the vaccine,” said Ruth Montgomery, associate professor of medicine at Yale School of Medicine and a co-author.
The researchers also found that the while the genes were predictive of a robust vaccine response in adults younger than age 35, those same genes did not improve responses in adults over age 60. “Another finding is that genes that contribute to good immune response are different in young and older people,” Montgomery noted.
“Surprisingly, we found that baseline differences, both at the gene and module level, were inversely correlated between young and older participants,” added Steven Kleinstein, associate professor of pathology at Yale School of Medicine and a corresponding author on the study. The reasons for these age differences warrant further study, said the researchers.
The findings offer new insights into the biology of vaccine response. They may also help investigators predict responses in individuals and develop strategies to improve vaccines, or treatments to boost the immune system’s response to vaccination, the researchers noted.

Yale University
news.yale.edu/2017/08/25/study-identifies-genes-linked-better-immune-response-flu-vaccine
 
 

Parkinson’s disease is an insidious disease: by the time it manifests as the typical motor dysfunctions such as tremors or muscle rigidity, portions of the brain have already been irreversibly destroyed. By this stage, the disease will have often begun already decades earlier. In search of an early portent of the disease, researchers led by Prof. Paul Wilmes, head of the Eco-Systems Biology Group at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg, may now have found one in the gut: they have shown that the bacterial community in the gut of Parkinson’s patients differs from that of healthy people even at a very early stage of the disease.
Experts have long been discussing the notion that Parkinson’s disease originates far outside the brain. According to the "dual hit" hypothesis, a hitherto unknown pathogen intrudes into the body through two ports of entry: the nose or the gastrointestinal tract. Once there, it sets a pathological process in motion, above all the misfolding of the protein alpha-synuclein. This is a protein whose exact function remains unknown. Among other things, it is presumed to be involved in the excretion of messengers such as dopamine. The misfolding of this protein could propagate through the nerve pathways, where – decades later – it produces the typical clumping in the dopaminergic cells, known as Lewy bodies, that are characteristic of Parkinson’s. Ultimately, nerve cells start to die off and the typical symptoms of Parkinson’s disease appear.
The researchers led by Wilmes, together with physicians Prof. Brit Mollenhauer and Prof. Wolfgang Oertel and their teams in Göttingen, Kassel and Marburg, explored the question of whether the early events in the course of the disease also change the bacterial community, the microbiome, at the two possible ports of entry. They took samples from the nose and gut of 76 Parkinson’s patients and 78 healthy control people who are taking part in a long-term study. They also examined the microbiome of 21 subjects diagnosed with iRBD, Idiopathic Rapid-Eye-Movement Sleep Behaviour Disorder. People with this sleep disorder have a greatly elevated risk of developing Parkinson’s disease later in life.
It turned out that the bacterial community of the gut differed considerably between all three groups. "Parkinson’s patients could be differentiated from healthy controls by their respective gut bacteria," explains the first author Dr. Anna Heintz-Buschart from the Eco-Systems Biology Group. And the majority of the differential bacteria showed similar trends in the iRBD group. For example, certain germs were more prevalent in one group while the count was lower in others. In the samples from the subjects’ nasal cavities, however, the researchers found no such differences. The study also revealed that certain gut microbes are associated with non-motor Parkinson’s symptoms, for example depression.
"We hope that, by comparing the groups, we will learn to better understand the role of the microbiome in the process of the disease and to find out what changes occur and when," Paul Wilmes explains. "This might deliver new starting points for early treatment of the disease. It would also be essential knowledge for one day being able to use the absence or presence of certain bacteria as a biomarker for early detection of the disease."

EurekAlert
www.eurekalert.org/pub_releases/2017-08/uol-abc082917.php

Gastric carcinoma is one of the most common causes of cancer-related deaths, primarily because most patients present at an advanced stage of the disease. The main cause of this cancer is the bacterium Helicobacter pylori, which chronically infects around half of all humans. However, unlike tumour viruses, bacteria do not deposit transforming genes in their host cells and how they are able to cause cancer has so far remained a mystery. An interdisciplinary research team at the Max Planck Institute in Berlin in collaboration with researchers in Stanford, California, has now discovered that the bacterium sends stem cell renewal in the stomach into overdrive – and stem cell turnover has been suspected by many scientists to play a role in the development of cancer. By showing that the stomach contains two different stem cell types, which respond differently to the same driver signal, they have uncovered a new mechanism of tissue plasticity. It allows tuning tissue renewal in response to bacterial infection.
While it has long been recognized that certain viruses can cause cancer by inserting oncogenes into the host cell DNA, the fact that some bacteria can also cause cancer has been slower to emerge and much harder to prove. While it is now clear that most cases of stomach cancer are linked to chronic infections with H. pylori, the mechanism remains unknown.
Thomas F. Meyer and his colleagues at the Max Planck Institute for Infection Biology in Berlin have spent many years investigating this bacterium and the changes it induces in the cells of the stomach epithelium. In particular, they were puzzled how malignancy could be induced in an environment in which cells are rapidly replaced. They suspected that the answer might lie in the stem cells found at the bottom of the glands that line the inside of the stomach, which continually replace the remaining cells ‘from the bottom up’ – and which are the only long-lived cells in the stomach. Michael Sigal, a clinical scientist of the Charité – Universitätsmedizin Berlin, who joined the Max Planck team, overturned the established dogma to show that H. pylori not only infects the surface cells, which are about to be sloughed off, but that some of the bacteria manage to invade deep into the glands and reach the stem cell compartment. They have now found that these stem cells do indeed respond to the infection by increasing their division – producing more cells and leading to the characteristic thickening of the mucosa observed in affected patients.
They used different transgenic mice to trace cells expressing particular genes, as well as all their daughter cells. The results indicate that the stomach glands contain two different stem cell populations. Both respond to a signalling molecule called Wnt, which maintains stem cell turnover in many adult tissues. Crucially, they discovered that myofibroblast cells in the connective tissue layer directly underneath the glands produce a second stem cell driver signal, R-spondin, to which the two stem cell populations responded differently. It is this signal, which turned out to control the response to H. pylori: following infection, the signal is ramped up, silencing the more slowly cycling stem cell population and putting the faster cycling stem cell population into overdrive.
These findings substantiate the rising awareness that chronic bacterial infections are strong promoters of cancer.

Max Planck Societyhttp://tinyurl.com/yaar3gcy

In a bid to detect cancers early and in a non-invasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to accurately identify more than half of 138 people with relatively early-stage colorectal, breast, lung and ovarian cancers. The test, the scientists say, is novel in that it can distinguish between DNA shed from tumours and other altered DNA that can be mistaken for cancer biomarkers.
 “This study shows that identifying cancer early using DNA changes in the blood is feasible and that our high accuracy sequencing method is a promising approach to achieve this goal,” says Victor Velculescu, M.D., Ph.D., professor of oncology at the Johns Hopkins Kimmel Cancer Center.
Blood tests for cancer are a growing part of clinical oncology, but they remain in the early stages of development. To find small bits of cancer-derived DNA in the blood of cancer patients, scientists have frequently relied on DNA alterations found in patients’ biopsied tumour samples as guideposts for the genetic mistakes they should be looking for among the masses of DNA circulating in those patients’ blood samples.
To develop a cancer screening test that could be used to screen seemingly healthy people, scientists had to find novel ways to spot DNA alterations that could be lurking in a person’s blood but had not been previously identified.
“The challenge was to develop a blood test that could predict the probable presence of cancer without knowing the genetic mutations present in a person’s tumour,” says Velculescu.
The goal, adds Jillian Phallen, a graduate student at the Johns Hopkins Kimmel Cancer Center who was involved in the research, was to develop a screening test that is highly specific for cancer and accurate enough to detect the cancer when present, while reducing the risk of “false positive” results that often lead to unnecessary over-testing and overtreatments.
The task is notably complicated, says Phallen, by the need to sort between true cancer-derived mutations and genetic alterations that occur in blood cells and as part of normal, inherited variations in DNA.
As blood cells divide, for example, Velculescu says there is a chance these cells will acquire mistakes or mutations. In a small fraction of people, these changes will spur a blood cell to multiply faster than its neighbouring cells, potentially leading to pre-leukemic conditions. However, most of the time, the blood-derived mutations are not cancer-initiating.
His team also ruled out so-called “germline” mutations. While germline mutations are indeed alterations in DNA, they occur as a result of normal variations between individuals, and are not usually linked to particular cancers.
To develop the new test, Velculescu, Phallen and their colleagues obtained blood samples from 200 patients with breast, lung, ovarian and colorectal cancer. The scientists’ blood test screened the patients’ blood samples for mutations within 58 genes widely linked to various cancers.
Overall, the scientists were able to detect 86 of 138 (62 percent) stage I and II cancers.   More specifically, among 42 people with colorectal cancer, the test correctly predicted cancer in half of the eight patients with stage I disease, eight of nine (89 percent) with stage II disease, nine of 10 (90 percent) with stage III and 14 of 15 (93 percent) with stage IV disease. Of 71 people with lung cancer, the scientists’ test identified cancer among 13 of 29 (45 percent) with stage I disease, 23 of 32 (72 percent) with stage II disease, three of four (75 percent) with stage III disease and five of six (83 percent) with stage IV cancer. For 42 patients with ovarian cancer, 16 of 24 (67 percent) with stage I disease were correctly identified, as well as three of four (75 percent) with stage II disease, six of eight (75 percent) with stage III cancer and five of six (83 percent) with stage IV disease. Among 45 breast cancer patients, the test spotted cancer-derived mutations in two of three (67 percent) patients with stage I disease, 17 of 29 (59 percent) with stage II disease and six of 13 (46 percent) with stage III cancers.
They found none of the cancer-derived mutations among blood samples of 44 healthy individuals.
Despite these initial promising results for early detection, the blood test needs to be validated in studies of much larger numbers of people, say the scientists.

John Hopkins Medicinehttp://tinyurl.com/yd8vb763