Tufts Medical Center researchers have shown that presence of a gene strongly linked to appetite regulation is highly predictive of a premature infant’s readiness to feed orally. An analysis of just a drop of an infant’s saliva could be the key to preventing many feeding problems and the expensive medical complications that can occur when infants are fed by mouth too early.
In a study Maron and colleagues have identified a biomarker in saliva that predicts a baby is not yet ready to feed 95 percent of the time. The biomarker, a gene for the neuropeptide Y2 receptor, NPY2R, is a known regulator of feeding behaviour. In their study, the researchers demonstrated that levels of NPY2R in saliva decline as a newborn matures enough to feed orally.
‘There’s a really important need for a better understanding and a more accurate assessment of infants’ feeding skills, ” said Jill L. Maron, MD, MPH, a researcher at the Mother Infant Research Institute at Tufts Medical Center. ‘Nearly every baby born early is at risk for feeding associated morbidities, which often lead to prolonged hospitalisations, short and long term health complications, and significant parental anxiety. This is a way of monitoring the most vulnerable babies very non-invasively. We can help guide clinical care without ever hurting them.”
Currently, caregivers use a variety of subjective measurements, such as evaluating a baby’s sucking and swallowing skills, to determine when it’s safe to feed a baby by mouth. But these methods are imprecise and often lead to feeding a baby too early, which can cause the child to choke, accidentally inhale breast milk or formula into their lungs leading to pneumonia, or other problems. Babies who suffer these early feeding difficulties can also go on to develop long-term feeding problems and are at risk of developmental delays. Research indicates that more than 40 percent of children in feeding disorder clinics were premature babies.
The NPY2R gene has been studied extensively because it helps regulate appetite and plays a role in both obesity and eating disorders. But no one had examined its role in prompting premature babies to eat, because most researchers were not focusing on appetite’s role in newborn feeding problems.
Tufts Medical Center
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By simply shining a tiny light within the small intestine, close to that organ’s junction with the pancreas, physicians at Mayo Clinic’s campus in Florida have been able to detect pancreatic cancer 100 percent of the time in a small study. The light, attached to a probe, measures changes in cells and blood vessels in the small intestine produced by a growing cancer in the adjoining pancreas.
This minimally invasive technique, called Polarisation Gating Spectroscopy, will now be tested in a much larger international clinical trial led by the Mayo Clinic researchers. The preliminary study suggests it may be possible, one day, to use a less invasive endoscope to screen patients for early development of pancreatic cancer.
The pancreas is notoriously hard to reach and see due to its very deep location in the abdomen, surrounded by intestines. The study investigators theorised that there may be changes in the nearby ‘normal appearing’ tissue of the small intestine which is much more accessible.
‘No one ever thought you could detect pancreatic cancer in an area that is somewhat remote from the pancreas, but this study suggests it may be possible,’ says Dr. Wallace, the chairman of the Division of Gastroenterology at Mayo Clinic in Florida. ‘Although results are still preliminary, the concept of detection field effects of nearby cancers holds great promise for possible early detection of pancreatic cancer.’
Pancreatic cancer is one of the most deadly of human tumours. It is only curable in 5 percent of cases, and even when it is surgically removed, 70 percent of patients have a recurrence that is fatal, Dr. Wallace says. There are no ways currently to detect the cancer early enough to cure a substantial number of patients, he says.
Pancreatic cancer is now usually detected through an imaging scan, followed by an invasive biopsy. Tumours found in this way are usually at an advanced stage.
In this study, the Mayo Clinic physicians tested a light probe developed by their long-time collaborators at Northwestern University.
The light, attached to a small fibre-optic probe known as an endoscope, measures the amount of oxygenated blood as well as the size of blood vessels in tissue near the duct where the pancreas joins the small intestine. Because a growing tumour requires a heightened supply of blood, normal tissue in the vicinity of the cancer
Mayo Clinic Arizona
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Children born with cleft lip, cleft palate and other craniofacial disorders face numerous medical challenges beyond appearance.
Patients can face serious airway, feeding, speech and hearing problems, as well as social and psychological challenges, Laura Swibel Rosenthal, MD, of Loyola University Medical Center and colleagues write.
‘The management of patients with craniofacial syndromes is complex,’ Rosenthal and colleagues write. ‘Otolaryngologic [ear-nose-throat] evaluation is of paramount importance in providing adequate care for this patient population.’
About 1 in 600 babies in the United States is born with a cleft lip and/or cleft palate, according to the Cleft Palate Foundation. The defect can range from a small notch in the lip to a grove that runs into the roof of the mouth. It can occur in isolation or in combination with other craniofacial birth defects. (A craniofacial disorder refers to an abnormality of the face and/or head.)
The first step in managing craniofacial patients is ensuring a safe airway. There’s also a great potential for nasal obstruction and sleep apnoea. And patients are at increased risk of developing upper airway problems such as sinusitis, laryngitis and rhinitis.
Hearing loss is common and often progressive. Thus, in addition to receiving standard newborn hearing screening, craniofacial patients should continue to receive periodic hearing tests, Rosenthal and colleagues write.
Craniofacial patients typically require several corrective surgeries, performed in staged fashion. Surgeons and anaesthesiologists should be aware of the potential challenges these patients may have with general anaesthesia.
The authors recommend a multidisciplinary approach, beginning with genetic counselling to determine the cause of the malformation, to inform parents about what to expect and to learn about the implications for other family members.
In addition to otolaryngologists, other specialists who typically care for craniofacial patients include pulmonologists, gastroenterologists, dentists and orthodontists. Depending on the congenital condition, a patient also may see pediatric specialists, such as cardiologists, ophthalmologists, neurosurgeons, endocrinologists, urologists, nephrologists and orthopaedic surgeons.
Most patients also need additional support services, including case management (social work), psychology or psychiatry, speech pathology, physical therapy, occupational therapy and other educational services.
Loyola University Health System
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The uproar that began last year when the U.S. Preventive Services Task Force stated that doctors should no longer offer regular prostate-cancer tests to healthy men continued this week when the task force released their final report. Overall, they stuck to their guns, stating that a blood test commonly used to screen for prostate cancer, the PSA test, causes more harm than good — it leads men to receive unnecessary, and sometimes even dangerous, treatments.
But many people simply don’t believe that the test is ineffective. Even faced with overwhelming evidence, such as a ten-year study of around 250,000 men that showed the test didn’t save lives, many activists and medical professionals are clamouring for men to continue receiving their annual PSA test. Why the disconnect?
In an article, researchers Hal R. Arkes, of Ohio State University, and Wolfgang Gaismaier, from the Max Planck Institute for Human Development in Berlin, Germany, picked apart lay-people’s reactions to the report, and examined the reasons why people are so reluctant to give up the PSA test.
‘Many folks who had a PSA test and think that it saved their life are infuriated that the Task Force seems to be so negative about the test,’ said Arkes.
They suggest several factors that may have contributed to the public’s condemnation of the report. Many studies have shown that anecdotes have power over a person’s perceptions of medical treatments. For example, a person can be shown statistics that Treatment A works less frequently than Treatment B, but if they read anecdotes (such as comments on a website) by other patients who had success with Treatment B, they’ll be more likely to pick Treatment B. The source of the anecdotes matters too. If a friend, a close relative, or any trusted source received successful treatment, they would be more likely to recommend that treatment to others, even if there was evidence showing the treatment only works for a minority of people.
Arkes and Gaismaier also propose that the public may have recoiled against the task force’s recommendations so fiercely because they weren’t able to properly evaluate the data in the report. Confusion over the use of control groups may have led people in the general public to weigh the data differently than medical professionals did.
‘How to change this is the million-dollar question,’ said Arkes. ‘Pictorial displays are far easier to comprehend than statistics. The two figures in our article depict the situation more clearly than text and numbers can do. I think data displayed in this manner can help change people’s view of the PSA test because we compare the relative outcomes of being tested and not being tested. Without that comparison, it is tough for the public to appreciate the relative pluses and minuses of the PSA test versus not having the PSA test.’
Men will be able to continue to request the PSA test, and it will be covered by health insurance for the foreseeable future. But psychological science suggests that unless people are convinced to choose statistics over anecdotes, confusion surrounding the test’s effectiveness will linger.
Association for Psychological Science
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A new study led by University of Kentucky researchers shows a new way to precisely detect a single chemical at extremely low concentrations and high contamination.
The study was carried out in the laboratory of Peixuan Guo, the William S. Farish Endowed Chair in Nanobiotechnology at the University of Kentucky Markey Cancer Center. The study shows that the phi29 DNA packaging nanomotor connector can be used to sense chemicals with reactive thioesters or maleimide using single channel conduction assays based on three observable fingerprints. This channel system could be further developed into very sensitive sensing devices.
The ability to detect a chemical at a low concentration and high contamination is especially important for environmental surveillance, homeland security, athlete drug monitoring, toxin/drug screening, and earlier disease diagnosis.
In the case of disease diagnosis, the production of an unusual metabolic product is a feature of disease, but in early stages, the concentration of this product is very low. Single molecule detection will facilitate the early detection of disease such as cancer, so as to facilitate earlier treatment.
‘Sensitivity of detection is a major challenge in the diagnosis of many diseases,’ said Guo. ‘Our next step is to find one metabolic product of one disease and determine the reality in earlier disease diagnosis.’
‘The proof-of-principle studies described in this study will be extended in the future to engineer multiple probes within a single pore for concurrent detection of multiple targets at the single molecule level in real time,’ said Farzin Haque, research assistant professor at the UK College of Pharmacy, and first author on the paper.
EurekAlert
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The Caterpillar got down off the mushroom … remarking as it went, ‘One side will make you grow taller, and the other side will make you grow shorter.’
—Lewis Carroll, ‘Alice’s Adventures in Wonderland’
UCLA geneticists have identified the mutation responsible for IMAGe syndrome, a rare disorder that stunts infants’ growth. The twist? The mutation occurs on the same gene that causes Beckwith–Wiedemann syndrome, which makes cells grow too fast, leading to very large children.
The UCLA findings could lead to new ways of blocking the rapid cell division that allows tumours to grow unchecked. The discovery also offers a new tool for diagnosing children with IMAGe syndrome, which until now has been difficult to identify accurately.
The discovery holds special significance for principal investigator Dr. Eric Vilain, a professor of human genetics, paediatrics and urology at the David Geffen School of Medicine at UCLA.
Nearly 20 years ago, as a medical resident in his native France, Vilain cared for two boys, ages 3 and 6, who were dramatically short for their ages. Though unrelated, the children shared a mysterious malady marked by minimal foetal development, stunted bone growth, sluggish adrenal glands, and undersized organs and genitals.
‘I never found a reason to explain these patients’ unusual set of symptoms,’ said Vilain, who also directs the UCLA Institute for Society and Genetics. ‘I’ve been searching for the cause of their disease since 1993.’
When Vilain joined UCLA as a genetics fellow, the two cases continued to intrigue him. His UCLA mentor at the time, geneticist Dr. Edward McCabe, recalled a similar case from his previous post at Baylor College of Medicine. The two of them obtained blood samples from the three cases and analysed the patients’ DNA for mutations in suspect genes but uncovered nothing.
Vilain and McCabe approached the Journal of Clinical Endocrinology and Metabolism and in 1999 published the first description of the syndrome, which they dubbed IMAGe, an acronym of sorts for the condition’s symptoms: intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia and genital anomalies.
Over the next decade, about 20 cases were reported around the world. But the cause of IMAGe syndrome remained a mystery.
Help arrived unexpectedly last year, when Vilain received an email from Argentinian physician Dr. Ignacio Bergada, who had unearthed the 1999 journal article. He told Vilain about a large family he was treating in which eight members suffered the same symptoms described in the study. All of the family members agreed to send their DNA samples to UCLA for study.
Vilain realized that he had stumbled across the scientific equivalent of winning the lottery. He assembled a team of UCLA researchers to partner with Bergada and London endocrinologist Dr. John Achermann.
‘At last, we had enough samples to help us zero in on the gene responsible for the syndrome,’ Vilain said. ‘Sequencing technology had also advanced in sophistication over the past two decades, allowing us to quickly analyse the entire family’s DNA samples.’
Vilain’s team performed a linkage study, which identifies disease-related genetic markers passed down from one generation to another. The results steered Vilain to a huge swath of Chromosome 11.
The UCLA Clinical Genomics Center performed next-generation sequencing, a powerful new technique that enabled the scientists to scour the enormous area in just two weeks and tease out a slender stretch that held the culprit mutation. The team also uncovered the same mutation in the original three cases described by Vilain and McCabe in 1999.
‘We discovered a mutation in a tiny sliver of the chromosome that appeared in every family member affected by IMAGe syndrome,’ Vilain said. ‘This was a big step forward. Now we can use gene sequencing as a tool to screen for the disease and diagnose children early enough for them to benefit from medical intervention.
‘We were a little surprised, because the mutation was located on a famous gene recognised for causing Beckwith–Wiedemann syndrome,’ he added. ‘The two diseases are polar opposites of each other.’
Children born with Beckwith–Wiedemann syndrome — named for the two doctors who discovered it — grow very large, with big adrenal glands, elongated bones and oversized internal organs. Because their cells grow so fast, one in five children with the disorder die of cancer at a young age. The disease appears in approximately one out of 15,000 births.
‘Finding opposite functions in the same gene is a rare biological phenomenon,’ Vilain emphasised. ‘When the mutation appeared in the slim section we identified, the infant developed IMAGe syndrome. If the mutation fell anywhere else in the gene, the child was born with Beckwith–Wiedemann. That’s really quite remarkable.’
UCLA
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Scientists have developed an ultra-sensitive test that should enable them to detect signs of a disease in its earliest stages.
The scientists, from Imperial College London and the University of Vigo, have created a test to detect particular molecules that indicate the presence of disease, even when these are in very low concentrations. There are already tests available for some diseases that look for such biomarkers using biological sensors or ’biosensors’. However, existing biosensors become less sensitive and predictable at detecting biomarkers when they are in very low concentrations, as occurs when a disease is in its early stages.
In this study, the researchers demonstrated that the new biosensor test can find a biomarker associated with prostate cancer, called Prostate Specific Antigen (PSA). However, the team say that the biosensor can be easily reconfigured to test for other diseases or viruses where the related biomarker is known.
Professor Molly Stevens, senior author of the study from the Departments of Materials and Bioengineering at Imperial College London, said: ‘It is vital to detect diseases at an early stage if we want people to have the best possible outcomes – diseases are usually easier to treat at this stage, and early diagnosis can give us the chance to halt a disease before symptoms worsen. However, for many diseases, using current technology to look for early signs of disease can be like finding the proverbial needle in a haystack. Our new test can actually find that needle. We only looked at the biomarker for one disease in this study, but we’re confident that the test can be adapted to identify many other diseases at an early stage.’
The team demonstrated the effectiveness of their biosensor by testing PSA biomarker samples in solutions containing a complex mixture of blood derived serum proteins. Monitoring the levels of PSA at ultralow concentrations can be crucial in the early diagnosis of the reoccurrence of prostate cancer, but classic detection approaches are not sensitive enough to carry out this analysis with a high degree of accuracy. The new test could enable more reliable diagnosis, but more research will need to be done to further explore its potential.
In their study, the team detected PSA at 0.000000000000000001 grams per millilitre, which is at the limits of current biosensor performance. By comparison, an existing test called an Enzyme-Linked Immunosorbent Assay (ELISA) test can detect PSA at 0.000000001 grams per millilitre, which is nine orders of magnitude more concentrated.
The biosensors used in today’s study consist of nanoscopic-sized gold stars floating in a solution containing other blood derived proteins. Attached to the surface of these gold stars are antibodies, which latch onto PSA when they detect it in a sample. A secondary antibody, which has an enzyme called glucose oxidase attached to it, recognises the PSA and creates a distinctive silver crystal coating on the gold stars, which is more apparent when the PSA biomarkers are in low concentrations. This silver coating acts like a signal that PSA is present, and it can be easily detected by scientists using optical microscopes.
The next stage of the research will see the team carrying out further clinical testing to assess the efficacy of the biosensor in detecting a range of different biomarkers associated with conditions such as HIV and other infections. They will also explore ways of commercialising their product.
Imperial College London
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For 5,000 years, the Chinese have used a system of medicine based on the flow and balance of positive and negative energies in the body. In this system, the appearance of the tongue is one of the measures used to classify the overall physical status of the body, or zheng. Now, University of Missouri researchers have developed computer software that combines the ancient practices and modern medicine by providing an automated system for analysing images of the tongue.
‘Knowing your zheng classification can serve as a pre-screening tool and help with preventive medicine,’ said Dong Xu, chair of MU’s computer science department in the College of Engineering and study co-author. ‘Our software helps bridge Eastern and Western medicine, since an imbalance in zheng could serve as a warning to go see a doctor. Within a year, our ultimate goal is to create an application for smartphones that will allow anyone to take a photo of their tongue and learn the status of their zheng.’
The software analyses images based on the tongue’s colour and coating to distinguish between tongues showing signs of ‘hot’ or ‘cold’ zheng. Shades of red and yellow are associated with hot zheng, whereas a white coating on the tongue is a sign of cold zheng.
‘Hot and cold zheng doesn’t refer directly to body temperature,’ said Xu, who is also on the faculty of the Bond Life Sciences Center. ‘Rather, it refers to a suite of symptoms associated with the state of the body as a whole.’
For example, a person with cold zheng may feel chills and coolness in the limbs and show a pale flushing of face. Their voice may have a high pitch. Other symptoms of cold sheng are clear urine and loose stool. They also may prefer hot foods and drinks and desire warm environments.
In Chinese traditional medicine both hot and cold zheng can be symptoms of gastritis, an inflammation of the stomach lining frequently caused by bacterial infection.
For the study, 263 gastritis patients and 48 healthy volunteers had their tongues analysed. The gastritis patients were classified by whether they showed infection by a certain bacteria, known as Helicobacter pylori, as well as the intensity of their gastritis symptoms. In addition, most of the gastritis patients had been previously classified with either hot or cold zheng. This allowed the researchers to verify the accuracy of the software’s analysis.
‘Our software was able to classify people based on their zheng status,’ said study co-author Ye Duan, associate professor of computer science at MU.
‘As we continue to work on the software we hope to improve its ability,’ Duan said. ‘Eventually everyone will be able to use this tool at home using webcams or smartphone applications. That will allow them to monitor their zheng and get an early warning about possible ailments.’
University of Missouri
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HER2 and its epidermal growth factor receptor cousins mobilise a specialised protein to activate a major player in cancer development and sugar metabolism, scientists report.
This chain of events, the scientists found, promotes Herceptin resistance in breast cancer and activation of glucose metabolism (glycolysis), which cancer cells primarily rely on to fuel their growth and survive.
Their research focused on Skp2 E3 ligase, a protein that binds to and tags other proteins with molecules called ubiquitins, in this case to activate the Akt kinase.
‘We discovered a novel function of Skp2 E3 ligase that makes it an important player in cancer development and also identified a crucial role for it as a regulator of the glycolysis pathway,’ said senior author Hui-Kuan Lin, Ph.D., associate professor in MD Anderson’s Department of Molecular and Cellular Oncology.
‘This is potentially important for understanding and addressing Herceptin resistance in breast cancer,’ Lin said. ‘The effect on glucose metabolism also could have implications for other types of solid tumour cancers, including prostate, because they rely so heavily on glycolysis.’
The team also found that Skp2 over-expression is associated with poor prognosis for breast cancer patients and its spread to other organs.
Lin and colleagues are studying potential inhibitors of Skp2 that might be developed for treatment.
The EGFR family of proteins includes HER2, which abundantly coats cancer cells in about a third of breast cancers, making these tumours prime targets for the targeted drug Herceptin.
The Akt kinase relays signals by growth factors from outside of the cell into the cell. It regulates cell proliferation and survival, metabolism and tumour development, the authors noted.
To do its work, whether normal or oncogenic signalling, it must move from the cytosol to the plasma membrane. To do that, Lin and colleagues had previously shown that Akt must be ubiquitinated – and those ubiquitins must be attached in a specific chain formation, the K63-linked polyubiquitin chains.
That earlier finding involved the insulin-like growth factor receptor (IGF-1) and a different E3 ligase. ‘Finding that the epidermal growth factor receptors also ubiquitinate Akt, and that they do so through the Skp2 E3 ligase, was quite unexpected,’ Lin said.
Finding two paths to ubiquitination implies that there might be more, Lin said.
University of Texas M. D. Anderson Cancer Center
Biomedical engineers at UC Davis have developed a microfluidic chip to test for latent tuberculosis. They hope the test will be cheaper, faster and more reliable than current testing for the disease.
‘Our assay is cheaper, reusable, and gives results in real time,’ said Ying Liu, a research specialist working with Professor Alexander Revzin in the UC Davis Department of Biomedical Engineering.
The team has already conducted testing of blood samples from patients in China and the United States.
About one-third of the world’s population is infected with the bacteria that cause tuberculosis, a disease that kills an estimated 1.5 million people worldwide every year, according to the U.S. Centers for Disease Control and Prevention.
Most infected people have latent TB, in which the bacteria are kept in check by the immune system. Patients become sick only when the immune system is compromised, enabling the bacteria to become active. People with HIV are at especially high risk.
Current tests for latent TB are based on detecting interferon-gamma, a disease-fighting chemical made by cells of the immune system. Commercially available tests require sending samples to a lab, and can be used just once.
Liu and Revzin used a novel approach: They coated a gold wafer with short pieces of a single-stranded DNA segment known to stick specifically to interferon-gamma. They then mounted the wafer in a chip that has tiny channels for blood samples. If interferon-gamma is present in a blood sample, it sticks to the DNA, triggering an electrical signal that can be read by a clinician.
‘If you see that the interferon-gamma level is high, you can diagnose latent TB,’ Liu said.
The researchers plan to refine the system so that the microfluidic sensor and electronic readout are integrated on a single chip.
UC Davis
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Researchers finds marker in premies’ saliva predicts readiness to feed by mouth
, /in E-News /by 3wmediaTufts Medical Center researchers have shown that presence of a gene strongly linked to appetite regulation is highly predictive of a premature infant’s readiness to feed orally. An analysis of just a drop of an infant’s saliva could be the key to preventing many feeding problems and the expensive medical complications that can occur when infants are fed by mouth too early.
In a study Maron and colleagues have identified a biomarker in saliva that predicts a baby is not yet ready to feed 95 percent of the time. The biomarker, a gene for the neuropeptide Y2 receptor, NPY2R, is a known regulator of feeding behaviour. In their study, the researchers demonstrated that levels of NPY2R in saliva decline as a newborn matures enough to feed orally.
‘There’s a really important need for a better understanding and a more accurate assessment of infants’ feeding skills, ” said Jill L. Maron, MD, MPH, a researcher at the Mother Infant Research Institute at Tufts Medical Center. ‘Nearly every baby born early is at risk for feeding associated morbidities, which often lead to prolonged hospitalisations, short and long term health complications, and significant parental anxiety. This is a way of monitoring the most vulnerable babies very non-invasively. We can help guide clinical care without ever hurting them.”
Currently, caregivers use a variety of subjective measurements, such as evaluating a baby’s sucking and swallowing skills, to determine when it’s safe to feed a baby by mouth. But these methods are imprecise and often lead to feeding a baby too early, which can cause the child to choke, accidentally inhale breast milk or formula into their lungs leading to pneumonia, or other problems. Babies who suffer these early feeding difficulties can also go on to develop long-term feeding problems and are at risk of developmental delays. Research indicates that more than 40 percent of children in feeding disorder clinics were premature babies.
The NPY2R gene has been studied extensively because it helps regulate appetite and plays a role in both obesity and eating disorders. But no one had examined its role in prompting premature babies to eat, because most researchers were not focusing on appetite’s role in newborn feeding problems. Tufts Medical Center
Pancreatic cancer may be detected with simple intestinal probe
, /in E-News /by 3wmediaBy simply shining a tiny light within the small intestine, close to that organ’s junction with the pancreas, physicians at Mayo Clinic’s campus in Florida have been able to detect pancreatic cancer 100 percent of the time in a small study. The light, attached to a probe, measures changes in cells and blood vessels in the small intestine produced by a growing cancer in the adjoining pancreas.
This minimally invasive technique, called Polarisation Gating Spectroscopy, will now be tested in a much larger international clinical trial led by the Mayo Clinic researchers. The preliminary study suggests it may be possible, one day, to use a less invasive endoscope to screen patients for early development of pancreatic cancer.
The pancreas is notoriously hard to reach and see due to its very deep location in the abdomen, surrounded by intestines. The study investigators theorised that there may be changes in the nearby ‘normal appearing’ tissue of the small intestine which is much more accessible.
‘No one ever thought you could detect pancreatic cancer in an area that is somewhat remote from the pancreas, but this study suggests it may be possible,’ says Dr. Wallace, the chairman of the Division of Gastroenterology at Mayo Clinic in Florida. ‘Although results are still preliminary, the concept of detection field effects of nearby cancers holds great promise for possible early detection of pancreatic cancer.’
Pancreatic cancer is one of the most deadly of human tumours. It is only curable in 5 percent of cases, and even when it is surgically removed, 70 percent of patients have a recurrence that is fatal, Dr. Wallace says. There are no ways currently to detect the cancer early enough to cure a substantial number of patients, he says.
Pancreatic cancer is now usually detected through an imaging scan, followed by an invasive biopsy. Tumours found in this way are usually at an advanced stage.
In this study, the Mayo Clinic physicians tested a light probe developed by their long-time collaborators at Northwestern University.
The light, attached to a small fibre-optic probe known as an endoscope, measures the amount of oxygenated blood as well as the size of blood vessels in tissue near the duct where the pancreas joins the small intestine. Because a growing tumour requires a heightened supply of blood, normal tissue in the vicinity of the cancer Mayo Clinic Arizona
Cleft lip and cleft palate causes much more that cosmetic problems
, /in E-News /by 3wmediaChildren born with cleft lip, cleft palate and other craniofacial disorders face numerous medical challenges beyond appearance.
Patients can face serious airway, feeding, speech and hearing problems, as well as social and psychological challenges, Laura Swibel Rosenthal, MD, of Loyola University Medical Center and colleagues write.
‘The management of patients with craniofacial syndromes is complex,’ Rosenthal and colleagues write. ‘Otolaryngologic [ear-nose-throat] evaluation is of paramount importance in providing adequate care for this patient population.’
About 1 in 600 babies in the United States is born with a cleft lip and/or cleft palate, according to the Cleft Palate Foundation. The defect can range from a small notch in the lip to a grove that runs into the roof of the mouth. It can occur in isolation or in combination with other craniofacial birth defects. (A craniofacial disorder refers to an abnormality of the face and/or head.)
The first step in managing craniofacial patients is ensuring a safe airway. There’s also a great potential for nasal obstruction and sleep apnoea. And patients are at increased risk of developing upper airway problems such as sinusitis, laryngitis and rhinitis.
Hearing loss is common and often progressive. Thus, in addition to receiving standard newborn hearing screening, craniofacial patients should continue to receive periodic hearing tests, Rosenthal and colleagues write.
Craniofacial patients typically require several corrective surgeries, performed in staged fashion. Surgeons and anaesthesiologists should be aware of the potential challenges these patients may have with general anaesthesia.
The authors recommend a multidisciplinary approach, beginning with genetic counselling to determine the cause of the malformation, to inform parents about what to expect and to learn about the implications for other family members.
In addition to otolaryngologists, other specialists who typically care for craniofacial patients include pulmonologists, gastroenterologists, dentists and orthodontists. Depending on the congenital condition, a patient also may see pediatric specialists, such as cardiologists, ophthalmologists, neurosurgeons, endocrinologists, urologists, nephrologists and orthopaedic surgeons.
Most patients also need additional support services, including case management (social work), psychology or psychiatry, speech pathology, physical therapy, occupational therapy and other educational services. Loyola University Health System
Psychological science explains uproar over prostate-cancer screenings
, /in E-News /by 3wmediaThe uproar that began last year when the U.S. Preventive Services Task Force stated that doctors should no longer offer regular prostate-cancer tests to healthy men continued this week when the task force released their final report. Overall, they stuck to their guns, stating that a blood test commonly used to screen for prostate cancer, the PSA test, causes more harm than good — it leads men to receive unnecessary, and sometimes even dangerous, treatments.
But many people simply don’t believe that the test is ineffective. Even faced with overwhelming evidence, such as a ten-year study of around 250,000 men that showed the test didn’t save lives, many activists and medical professionals are clamouring for men to continue receiving their annual PSA test. Why the disconnect?
In an article, researchers Hal R. Arkes, of Ohio State University, and Wolfgang Gaismaier, from the Max Planck Institute for Human Development in Berlin, Germany, picked apart lay-people’s reactions to the report, and examined the reasons why people are so reluctant to give up the PSA test.
‘Many folks who had a PSA test and think that it saved their life are infuriated that the Task Force seems to be so negative about the test,’ said Arkes.
They suggest several factors that may have contributed to the public’s condemnation of the report. Many studies have shown that anecdotes have power over a person’s perceptions of medical treatments. For example, a person can be shown statistics that Treatment A works less frequently than Treatment B, but if they read anecdotes (such as comments on a website) by other patients who had success with Treatment B, they’ll be more likely to pick Treatment B. The source of the anecdotes matters too. If a friend, a close relative, or any trusted source received successful treatment, they would be more likely to recommend that treatment to others, even if there was evidence showing the treatment only works for a minority of people.
Arkes and Gaismaier also propose that the public may have recoiled against the task force’s recommendations so fiercely because they weren’t able to properly evaluate the data in the report. Confusion over the use of control groups may have led people in the general public to weigh the data differently than medical professionals did.
‘How to change this is the million-dollar question,’ said Arkes. ‘Pictorial displays are far easier to comprehend than statistics. The two figures in our article depict the situation more clearly than text and numbers can do. I think data displayed in this manner can help change people’s view of the PSA test because we compare the relative outcomes of being tested and not being tested. Without that comparison, it is tough for the public to appreciate the relative pluses and minuses of the PSA test versus not having the PSA test.’
Men will be able to continue to request the PSA test, and it will be covered by health insurance for the foreseeable future. But psychological science suggests that unless people are convinced to choose statistics over anecdotes, confusion surrounding the test’s effectiveness will linger. Association for Psychological Science
New study shows how nanotechnology can help detect disease earlier
, /in E-News /by 3wmediaA new study led by University of Kentucky researchers shows a new way to precisely detect a single chemical at extremely low concentrations and high contamination.
The study was carried out in the laboratory of Peixuan Guo, the William S. Farish Endowed Chair in Nanobiotechnology at the University of Kentucky Markey Cancer Center. The study shows that the phi29 DNA packaging nanomotor connector can be used to sense chemicals with reactive thioesters or maleimide using single channel conduction assays based on three observable fingerprints. This channel system could be further developed into very sensitive sensing devices.
The ability to detect a chemical at a low concentration and high contamination is especially important for environmental surveillance, homeland security, athlete drug monitoring, toxin/drug screening, and earlier disease diagnosis.
In the case of disease diagnosis, the production of an unusual metabolic product is a feature of disease, but in early stages, the concentration of this product is very low. Single molecule detection will facilitate the early detection of disease such as cancer, so as to facilitate earlier treatment.
‘Sensitivity of detection is a major challenge in the diagnosis of many diseases,’ said Guo. ‘Our next step is to find one metabolic product of one disease and determine the reality in earlier disease diagnosis.’
‘The proof-of-principle studies described in this study will be extended in the future to engineer multiple probes within a single pore for concurrent detection of multiple targets at the single molecule level in real time,’ said Farzin Haque, research assistant professor at the UK College of Pharmacy, and first author on the paper. EurekAlert
Disease that stunts infants’ growth traced to same gene that makes kids grow too fast
, /in E-News /by 3wmediaThe Caterpillar got down off the mushroom … remarking as it went, ‘One side will make you grow taller, and the other side will make you grow shorter.’
—Lewis Carroll, ‘Alice’s Adventures in Wonderland’
UCLA geneticists have identified the mutation responsible for IMAGe syndrome, a rare disorder that stunts infants’ growth. The twist? The mutation occurs on the same gene that causes Beckwith–Wiedemann syndrome, which makes cells grow too fast, leading to very large children.
The UCLA findings could lead to new ways of blocking the rapid cell division that allows tumours to grow unchecked. The discovery also offers a new tool for diagnosing children with IMAGe syndrome, which until now has been difficult to identify accurately.
The discovery holds special significance for principal investigator Dr. Eric Vilain, a professor of human genetics, paediatrics and urology at the David Geffen School of Medicine at UCLA.
Nearly 20 years ago, as a medical resident in his native France, Vilain cared for two boys, ages 3 and 6, who were dramatically short for their ages. Though unrelated, the children shared a mysterious malady marked by minimal foetal development, stunted bone growth, sluggish adrenal glands, and undersized organs and genitals.
‘I never found a reason to explain these patients’ unusual set of symptoms,’ said Vilain, who also directs the UCLA Institute for Society and Genetics. ‘I’ve been searching for the cause of their disease since 1993.’
When Vilain joined UCLA as a genetics fellow, the two cases continued to intrigue him. His UCLA mentor at the time, geneticist Dr. Edward McCabe, recalled a similar case from his previous post at Baylor College of Medicine. The two of them obtained blood samples from the three cases and analysed the patients’ DNA for mutations in suspect genes but uncovered nothing.
Vilain and McCabe approached the Journal of Clinical Endocrinology and Metabolism and in 1999 published the first description of the syndrome, which they dubbed IMAGe, an acronym of sorts for the condition’s symptoms: intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia and genital anomalies.
Over the next decade, about 20 cases were reported around the world. But the cause of IMAGe syndrome remained a mystery.
Help arrived unexpectedly last year, when Vilain received an email from Argentinian physician Dr. Ignacio Bergada, who had unearthed the 1999 journal article. He told Vilain about a large family he was treating in which eight members suffered the same symptoms described in the study. All of the family members agreed to send their DNA samples to UCLA for study.
Vilain realized that he had stumbled across the scientific equivalent of winning the lottery. He assembled a team of UCLA researchers to partner with Bergada and London endocrinologist Dr. John Achermann.
‘At last, we had enough samples to help us zero in on the gene responsible for the syndrome,’ Vilain said. ‘Sequencing technology had also advanced in sophistication over the past two decades, allowing us to quickly analyse the entire family’s DNA samples.’
Vilain’s team performed a linkage study, which identifies disease-related genetic markers passed down from one generation to another. The results steered Vilain to a huge swath of Chromosome 11.
The UCLA Clinical Genomics Center performed next-generation sequencing, a powerful new technique that enabled the scientists to scour the enormous area in just two weeks and tease out a slender stretch that held the culprit mutation. The team also uncovered the same mutation in the original three cases described by Vilain and McCabe in 1999.
‘We discovered a mutation in a tiny sliver of the chromosome that appeared in every family member affected by IMAGe syndrome,’ Vilain said. ‘This was a big step forward. Now we can use gene sequencing as a tool to screen for the disease and diagnose children early enough for them to benefit from medical intervention.
‘We were a little surprised, because the mutation was located on a famous gene recognised for causing Beckwith–Wiedemann syndrome,’ he added. ‘The two diseases are polar opposites of each other.’
Children born with Beckwith–Wiedemann syndrome — named for the two doctors who discovered it — grow very large, with big adrenal glands, elongated bones and oversized internal organs. Because their cells grow so fast, one in five children with the disorder die of cancer at a young age. The disease appears in approximately one out of 15,000 births.
‘Finding opposite functions in the same gene is a rare biological phenomenon,’ Vilain emphasised. ‘When the mutation appeared in the slim section we identified, the infant developed IMAGe syndrome. If the mutation fell anywhere else in the gene, the child was born with Beckwith–Wiedemann. That’s really quite remarkable.’ UCLA
Super-sensitive tests could detect diseases earlier
, /in E-News /by 3wmediaScientists have developed an ultra-sensitive test that should enable them to detect signs of a disease in its earliest stages.
The scientists, from Imperial College London and the University of Vigo, have created a test to detect particular molecules that indicate the presence of disease, even when these are in very low concentrations. There are already tests available for some diseases that look for such biomarkers using biological sensors or ’biosensors’. However, existing biosensors become less sensitive and predictable at detecting biomarkers when they are in very low concentrations, as occurs when a disease is in its early stages.
In this study, the researchers demonstrated that the new biosensor test can find a biomarker associated with prostate cancer, called Prostate Specific Antigen (PSA). However, the team say that the biosensor can be easily reconfigured to test for other diseases or viruses where the related biomarker is known.
Professor Molly Stevens, senior author of the study from the Departments of Materials and Bioengineering at Imperial College London, said: ‘It is vital to detect diseases at an early stage if we want people to have the best possible outcomes – diseases are usually easier to treat at this stage, and early diagnosis can give us the chance to halt a disease before symptoms worsen. However, for many diseases, using current technology to look for early signs of disease can be like finding the proverbial needle in a haystack. Our new test can actually find that needle. We only looked at the biomarker for one disease in this study, but we’re confident that the test can be adapted to identify many other diseases at an early stage.’
The team demonstrated the effectiveness of their biosensor by testing PSA biomarker samples in solutions containing a complex mixture of blood derived serum proteins. Monitoring the levels of PSA at ultralow concentrations can be crucial in the early diagnosis of the reoccurrence of prostate cancer, but classic detection approaches are not sensitive enough to carry out this analysis with a high degree of accuracy. The new test could enable more reliable diagnosis, but more research will need to be done to further explore its potential.
In their study, the team detected PSA at 0.000000000000000001 grams per millilitre, which is at the limits of current biosensor performance. By comparison, an existing test called an Enzyme-Linked Immunosorbent Assay (ELISA) test can detect PSA at 0.000000001 grams per millilitre, which is nine orders of magnitude more concentrated.
The biosensors used in today’s study consist of nanoscopic-sized gold stars floating in a solution containing other blood derived proteins. Attached to the surface of these gold stars are antibodies, which latch onto PSA when they detect it in a sample. A secondary antibody, which has an enzyme called glucose oxidase attached to it, recognises the PSA and creates a distinctive silver crystal coating on the gold stars, which is more apparent when the PSA biomarkers are in low concentrations. This silver coating acts like a signal that PSA is present, and it can be easily detected by scientists using optical microscopes.
The next stage of the research will see the team carrying out further clinical testing to assess the efficacy of the biosensor in detecting a range of different biomarkers associated with conditions such as HIV and other infections. They will also explore ways of commercialising their product. Imperial College London
Tongue analysis software developed at MU uses ancient Chinese medicine to warn of disease
, /in E-News /by 3wmediaFor 5,000 years, the Chinese have used a system of medicine based on the flow and balance of positive and negative energies in the body. In this system, the appearance of the tongue is one of the measures used to classify the overall physical status of the body, or zheng. Now, University of Missouri researchers have developed computer software that combines the ancient practices and modern medicine by providing an automated system for analysing images of the tongue.
‘Knowing your zheng classification can serve as a pre-screening tool and help with preventive medicine,’ said Dong Xu, chair of MU’s computer science department in the College of Engineering and study co-author. ‘Our software helps bridge Eastern and Western medicine, since an imbalance in zheng could serve as a warning to go see a doctor. Within a year, our ultimate goal is to create an application for smartphones that will allow anyone to take a photo of their tongue and learn the status of their zheng.’
The software analyses images based on the tongue’s colour and coating to distinguish between tongues showing signs of ‘hot’ or ‘cold’ zheng. Shades of red and yellow are associated with hot zheng, whereas a white coating on the tongue is a sign of cold zheng.
‘Hot and cold zheng doesn’t refer directly to body temperature,’ said Xu, who is also on the faculty of the Bond Life Sciences Center. ‘Rather, it refers to a suite of symptoms associated with the state of the body as a whole.’
For example, a person with cold zheng may feel chills and coolness in the limbs and show a pale flushing of face. Their voice may have a high pitch. Other symptoms of cold sheng are clear urine and loose stool. They also may prefer hot foods and drinks and desire warm environments.
In Chinese traditional medicine both hot and cold zheng can be symptoms of gastritis, an inflammation of the stomach lining frequently caused by bacterial infection.
For the study, 263 gastritis patients and 48 healthy volunteers had their tongues analysed. The gastritis patients were classified by whether they showed infection by a certain bacteria, known as Helicobacter pylori, as well as the intensity of their gastritis symptoms. In addition, most of the gastritis patients had been previously classified with either hot or cold zheng. This allowed the researchers to verify the accuracy of the software’s analysis.
‘Our software was able to classify people based on their zheng status,’ said study co-author Ye Duan, associate professor of computer science at MU.
‘As we continue to work on the software we hope to improve its ability,’ Duan said. ‘Eventually everyone will be able to use this tool at home using webcams or smartphone applications. That will allow them to monitor their zheng and get an early warning about possible ailments.’ University of Missouri
Skp2 activates cancer-promoting, glucose-processing Akt
, /in E-News /by 3wmediaHER2 and its epidermal growth factor receptor cousins mobilise a specialised protein to activate a major player in cancer development and sugar metabolism, scientists report.
This chain of events, the scientists found, promotes Herceptin resistance in breast cancer and activation of glucose metabolism (glycolysis), which cancer cells primarily rely on to fuel their growth and survive.
Their research focused on Skp2 E3 ligase, a protein that binds to and tags other proteins with molecules called ubiquitins, in this case to activate the Akt kinase.
‘We discovered a novel function of Skp2 E3 ligase that makes it an important player in cancer development and also identified a crucial role for it as a regulator of the glycolysis pathway,’ said senior author Hui-Kuan Lin, Ph.D., associate professor in MD Anderson’s Department of Molecular and Cellular Oncology.
‘This is potentially important for understanding and addressing Herceptin resistance in breast cancer,’ Lin said. ‘The effect on glucose metabolism also could have implications for other types of solid tumour cancers, including prostate, because they rely so heavily on glycolysis.’
The team also found that Skp2 over-expression is associated with poor prognosis for breast cancer patients and its spread to other organs.
Lin and colleagues are studying potential inhibitors of Skp2 that might be developed for treatment.
The EGFR family of proteins includes HER2, which abundantly coats cancer cells in about a third of breast cancers, making these tumours prime targets for the targeted drug Herceptin.
The Akt kinase relays signals by growth factors from outside of the cell into the cell. It regulates cell proliferation and survival, metabolism and tumour development, the authors noted.
To do its work, whether normal or oncogenic signalling, it must move from the cytosol to the plasma membrane. To do that, Lin and colleagues had previously shown that Akt must be ubiquitinated – and those ubiquitins must be attached in a specific chain formation, the K63-linked polyubiquitin chains.
That earlier finding involved the insulin-like growth factor receptor (IGF-1) and a different E3 ligase. ‘Finding that the epidermal growth factor receptors also ubiquitinate Akt, and that they do so through the Skp2 E3 ligase, was quite unexpected,’ Lin said.
Finding two paths to ubiquitination implies that there might be more, Lin said. University of Texas M. D. Anderson Cancer Center
New TB test promises to be cheap and fast
, /in E-News /by 3wmediaBiomedical engineers at UC Davis have developed a microfluidic chip to test for latent tuberculosis. They hope the test will be cheaper, faster and more reliable than current testing for the disease.
‘Our assay is cheaper, reusable, and gives results in real time,’ said Ying Liu, a research specialist working with Professor Alexander Revzin in the UC Davis Department of Biomedical Engineering.
The team has already conducted testing of blood samples from patients in China and the United States.
About one-third of the world’s population is infected with the bacteria that cause tuberculosis, a disease that kills an estimated 1.5 million people worldwide every year, according to the U.S. Centers for Disease Control and Prevention.
Most infected people have latent TB, in which the bacteria are kept in check by the immune system. Patients become sick only when the immune system is compromised, enabling the bacteria to become active. People with HIV are at especially high risk.
Current tests for latent TB are based on detecting interferon-gamma, a disease-fighting chemical made by cells of the immune system. Commercially available tests require sending samples to a lab, and can be used just once.
Liu and Revzin used a novel approach: They coated a gold wafer with short pieces of a single-stranded DNA segment known to stick specifically to interferon-gamma. They then mounted the wafer in a chip that has tiny channels for blood samples. If interferon-gamma is present in a blood sample, it sticks to the DNA, triggering an electrical signal that can be read by a clinician.
‘If you see that the interferon-gamma level is high, you can diagnose latent TB,’ Liu said.
The researchers plan to refine the system so that the microfluidic sensor and electronic readout are integrated on a single chip. UC Davis