Rheumatoid arthritis (RA) is an autoimmune disorder that occurs when the immune system mistakenly attacks the body’s tissues. Unlike the wear-and-tear damage of osteoarthritis, rheumatoid arthritis affects the lining of the joints, causing painful swelling that can eventually result in bone erosion and joint deformity.
Most RA patients are positive for anticitrullinated protein antibodies (ACPA), and these antibodies are highly specific for RA diagnosis. ACPA recognizes various citrullinated proteins, such as fibrinogen, vimentin and glucose- 6-phosphate isomerase. Citrullinated proteins are proteins that have the amino acid arginine converted into the citrulline, which is not one of the 20 standard amino acids encoded by DNA in the genetic code. Autoreactivity to citrullinated protein may increase susceptibility to RA.
While many candidate citrullinated antigens have been identified in RA joints, the involvement of citrullinated proteins in blood serum remains mostly uninvestigated. To that end, a team of University of Tsukuba-centred researchers set out to explore the expression and commonality of citrullinated proteins in peptide glucose-6-phosphate isomerase-induced arthritis (pGIA) and patients with RA, and went one step further to investigate its correlation with RA disease activity.
“We examined serum citrullinated proteins from pGIA by western blotting, and the sequence was identified by mass spectrometry. With the same methods, serum citrullinated proteins were analysed in patients with RA, primary Sjögren’s syndrome, systemic lupus erythematosus, and osteoarthritis as well as in healthy subjects,” study corresponding author Isao Matsumoto explains. “In patients with RA, the relationship between the expression of the identified protein inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) and clinical features was also evaluated, and the levels of citrullinated ITIH4 were compared before and after biological treatment.”
The researchers found that citrullinated ITIH4 was highly specific to patients with RA, compared with patients with other autoimmune and arthritic diseases or in healthy subjects, indicating a potential role for citrullinated ITIH4 in RA pathogenesis. Notably, its levels were decreased in correlation with the reduction of disease activity score after effective treatment in patients with RA. Moreover, antibody response to citrullinated epitope in ITIH4 was specifically observed in patients with RA.
“Our results suggest that citrullinated ITIH4 might be a novel biomarker to distinguish RA from other rheumatic diseases and for assessing disease activity in patients with RA,” Matsumoto says. “To our knowledge, this is the first report of its kind in the literature.”

MedicalXpresshttps://medicalxpress.com

An international team of researchers from the Hopp Children’s Cancer Centre at the NCT Heidelberg (KiTZ), the European Molecular Biology Laboratory (EMBL) and the German Cancer Consortium (DKTK) together with colleagues at the St. Jude Children’s Research Hospital in Memphis and the Hospital for Sick Children in Toronto has summarized hereditary gene defects which can trigger the development of certain malignant brain tumours (medulloblastoma). From their findings, the team has derived recommendations for routine genetic screening in medulloblastoma patients. Medulloblastoma is a rare malignant tumour of the cerebellum and occurs predominantly in children. Scientists believe that in many cases hereditary gene defects trigger the development of this malignant disease. However, there are no standards for routine genetic screening of patients, nor are there guidelines and a corresponding nationwide infrastructure for genetic counselling of affected families.
Scientists have now been able to characterize medulloblastoma more accurately and to derive recommendations for genetic testing based on analysis of 1022 patients with medulloblastoma. “We analysed genes that have been previously implicated in predisposition to any type of pediatric and adult cancer”, says Sebastian Waszak from the EMBL Heidelberg who is one of the study’s lead authors. It turned out that six genes were also frequently affected by genetic alterations in patients with medulloblastoma.
Considering the six significantly enriched genes, about five percent of patients had an increased risk of cancer. Taking into account all cancer risk genes, about eleven percent of the patients had an increased cancer risk. Looking at a particular tumour subgroup, the so called “SHH-activated medulloblastoma”, even 20 percent were identified to harbour a genetic predisposition to cancer.
These predisposing mutations occur in every single cell of the patient and can be also passed on to offspring. “Mutations of this kind often indicate a familial predisposition to cancer and therefore place special demands on the treatment of patients and the counselling of families”, said Paul Northcott from the St. Jude Children’s Research Hospital in Memphis, who shares the lead authorship. The results are particularly important because both materials from previous studies and patient data from four current or recently completed clinical trials were included in the analysis.
Based on these findings and other tumour features, the scientists developed criteria for routine genetic screening. “Hereditary disease factors usually have a significant impact on the whole family of the patient, We want to make genetic analysis available as a standard of care for patients with specific medulloblastoma”, says Stefan Pfister, KiTZ director, scientist at the German Cancer Research Centre, and senior physician at the Heidelberg University Hospital. To make this possible, Stefan Pfister and Christian Kratz from the Hannover Medical School have created a registry for patients with a hereditary cancer predisposition and a website that contains information for patients, families, and physicians (www.krebs-praedisposition.de).

The German Cancer Research Center (DKFZ)https://tinyurl.com/ya5akv4j

The longest FlexLab automation system ever produced by Inpeco has been designed for a mega volume reference laboratory customer, Hermes Pardini group based in Minas Gerais, Brazil. Siemens Healthineers (Inpeco’s strategic automation partner who sold the solution) is implementing the FlexLab system for Hermes Pardini’s “Enterprise” project, which will result in the largest laboratory automation platform in the world, linking more than 100 analyzers and 7 clinical specialties.
The Hermes Pardini Group is highly innovative in diagnostics medicine, and will handle 110 million sample tubes every year to address diagnostic testing needs of patients and healthcare providers from all across Brazil. The Enterprise project is expected to be operating at its full capacity in 2019, and will automate the distribution of sample tubes to nearly 100 different analyzers with a total length of 330 meters, which will include more than 70 pre- and postanalytical modules to eliminate the need for error-prone and time-consuming manual interventions within the clinical laboratory. It is to be installed in the Vespasiano site (Belo Horizonte area) in the current laboratory testing area (3,500 square meters of floor space).
“Unlike conventional laboratory set-ups, where sample tubes must be moved manually between different analyzers, our enterprise lab will employ a ‘one-touch, one workflow’ concept to eliminate the need for manual interventions, ensure sample traceability, and reduce the turnaround time to results,” said Guilherme Collares, Chief Operations Officer of the Hermes Pardini Group.
Inpeco’s High Throughput FlexLab solution will contribute to make this concept a reality, and enable providers to receive results faster, thereby enabling better patient care. The project also includes refrigerated storage units, with capacity to hold more than 1.3 million samples, and a newly developed advanced vision system, which is able to detect sample deterioration such as hemolysis, icterus or lipemia. “We’ve been in touch with Hermes Pardini since they began 2 evaluating options to replace the automation system they were using – said Andrea Pedrazzini, President of Inpeco – and we are extremely proud and pleased that such a prestigious institution has decided to adopt the largest FlexLab system ever built to fully automate their samples process, from loading to storing and disposing.”

http://www.inpeco.com/en/

A multidisciplinary team at NUS BIGHEART has developed enVision – a portable, easy-to-use and inexpensive device for quick and accurate screening of diseases.
enVision takes between 30 minutes to one hour to detect the presence of diseases, which is two to four times faster than existing infection diagnostics methods. In addition, each test kit costs under S$1 – 100 times lower than the current cost of conducting similar tests.
“The enVision platform is extremely sensitive, accurate, fast, and low-cost. It works at room temperature and does not require heaters or special pumps, making it very portable. With this invention, tests can be done at the point-of-care, for instance in community clinics or hospital wards, so that disease monitoring or treatment can be administered in a timely manner to achieve better health outcomes,” said team leader Assistant Professor Shao Huilin from the Biomedical Institute for Global Health Research and Technology (BIGHEART) and Department of Biomedical Engineering at NUS. Asst Prof Shao is also an investigator with the Institute of Molecular and Cell Biology (IMCB) under the Agency for Science, Technology and Research (A*STAR).
The research team used the human papillomavirus (HPV), the key cause of cervical cancer, as a clinical model to validate the performance of enVision. In comparison to clinical gold standard, this novel technology has demonstrated superior sensitivity and specificity.
“enVision is not only able to accurately detect different subtypes of the same disease, it is also able to spot differences within a specific subtype of a given disease to identify previously undetectable infections," Asst Prof Shao added.
In addition, test results are easily visible – the assay turns from colourless to brown if a disease is present – and could also be further analysed using a smartphone for quantitative assessment of the amount of pathogen present. This makes enVision an ideal solution for personal healthcare and telemedicine.
“Conventional technologies – such as tests that rely on polymerase chain reaction to amplify and detect specific DNA molecules – require bulky and expensive equipment, as well as trained personnel to operate these machines. With enVision, we are essentially bringing the clinical laboratory to the patient. Minimal training is needed to administer the ,test and interpret the results, so more patients can have access to effective, lab-quality diagnostics that will substantially improve the quality of care and treatment,” said Dr Nicholas Ho, a researcher from NUS BIGHEART and A*STAR’s IMCB, and co-first author of the study.

National University of Singapore
news.nus.edu.sg/press-releases/envision-device-for-disease-screening

A new way to assess the impact of normal ageing on bones, joints and muscles has been proposed that could provide a benchmark for how well older people are able to keep moving.
The composition of the body changes as we get older, as muscle strength and bone density decline. But the challenge to date has been distinguishing between the normal effects of ageing and the first signs of disease.
As a result there has been limited consensus on appropriate biomarkers of normal ageing. This has led to an unreliable picture of musculoskeletal health in older people as bone, joints and muscle have been looked at in isolation, not as a complete system.
To address this, experts at the Medical Research Council-Arthritis UK Centre for Integrated Research into Musculoskeletal Ageing (CIMA) – a collaboration between Newcastle, Liverpool and Sheffield universities – have now proposed a set of measurements that can be used as a toolkit to assess bone, joint and muscle health.
The CIMA team say that the new toolkit will provide a consistent and holistic way to measure the gradual loss of function that everyone experiences as we get older.
In particular, they recommend the use of two biomarkers to assess bone condition – PINP and CTX, both well-established indicators of bone turnover. High levels of these biomarkers are often associated with greater fracture risk and faster rates of bone loss, particularly in older women.
The toolkit also proposes reliable indicators of cartilage damage, muscle mass, body composition and assessment of functional capability.
Professor John Mathers, from Newcastle University’s Institute for Ageing, said: “We know that when older people have limited mobility or stop being active altogether it can have a significant, negative impact on their cardio-vascular health, their neurological health and their quality of life overall, increasing the risk of disease.
“This new toolkit will help us better understand how well the whole musculoskeletal system functions as we age so that we can help people stay physically active and healthy for longer.”
The toolkit is a first step towards a comprehensive framework that could be used by researchers and clinicians – both with individuals as needed and, potentially, as part of a public health screening programme for older people.
Over time, this could identify parameters for normal musculoskeletal ageing according to gender and age. To aid this, the CIMA team say that the toolkit could be used earlier – when people are in their 50s and early 60s, before age-related disease or disability can occur – in order to get a better picture of how the musculoskeletal system ages.

Newcastle University
www.ncl.ac.uk/press/articles/latest/2018/09/toolkittoassessmusculoskeletalhealth/