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Archive for category: E-News

E-News

A mammal lung, in 3D

, 26 August 2020/in E-News /by 3wmedia

A research team led by the University of Iowa has created the most detailed, three-dimensional rendering of a mammal lung…Amidst the extraordinarily dense network of pathways in a mammal lung is a common destination. There, any road leads to a cul-de-sac of sorts called the pulmonary acinus. This place looks like a bunch of grapes attached to a stem (acinus means ‘berry’ in Latin).
Scientists have struggled to understand more specifically what happens in this microscopic, labyrinthine intersection of alleys and dead ends. To find out, a research team led by the University of Iowa created the most detailed, three-dimensional rendering of the pulmonary acinus. The computerised model, derived from mice, faithfully mimics each twist and turn in this region, including the length, direction and angles of the respiratory branches that lead to the all-important air sacs called alveoli.
 
The model is important, because it can help scientists understand where and how lung diseases emerge as well as the role the pulmonary acinus plays in the delivery of drugs, such as those commonly administered with inhalers.
‘These methods allow us to understand where in the lung periphery disease begins and how it progresses,’ says Eric Hoffman, professor in the departments of radiology, medicine, and biomedical engineering at the UI and corresponding author on the paper. ‘How do gases and inhaled substances get there and do they accumulate in one or another acinus? How do they swirl around and clear out? We just don’t have a complete understanding how that happens.’
As an example, Hoffman said the model could be used to determine how smoking-induced emphysema originates. ‘It has been hypothesised recently that it begins with the loss of peripheral airways rather than the lung air sacs,’ he says, citing ongoing research by James Hogg at the University of British Columbia, who was not involved in this study. It also could shed light and lead to more effective treatment of chronic obstructive pulmonary disease, which causes irreversible damage to the lung, says Dragos Vasilescu, first author on the paper who based his thesis on the research while a graduate student at the UI.
For years, the best that lung anatomy pioneers such as study co-corresponding author Ewald Weibel, professor emeritus of anatomy at the University of Bern, could do to study specific areas of a lung was to make measurements in two dimensions or create 3D casts of a lung’s air spaces. The techniques, while giving the earliest insights into a lungs’s makeup and functioning, had their limitations. For one, they did not directly replicate a lung’s structure in real life, and they could not convey how various parts act together as a whole. Yet advances in imaging and computation have enabled researchers to more fully explore how gases and other inhaled substances act in the lung’s furthest recesses.
In this study, the team worked with 22 pulmonary acini culled from young and old mice. They then set to ‘reconstruct’ the acini based on micro computed tomography imaging of scanned lungs in mice and extracted from them. The extracted lungs were preserved in a way that kept the anatomy intact—including the tiny air spaces required for successful imaging. From that, the researchers were able to measure an acinus, estimate the number of acini for each mouse lung and even count the alveoli and measure their surface area.
The mouse lung, in its structure and function, is remarkably similar to the human lung. That means researchers can alter the genetics of a mouse and see how those changes affect the peripheral structure of the lung and its performance.
Already, the researchers found in the current study that mouse alveoli increase in number long past the two weeks that at least one previous study had indicated. Hoffman adds that a separate study is needed to determine whether humans, too, increase the number of air sacs past a certain, predetermined age.
The researchers next aim to use the model to more fully understand how gases interact with the bloodstream within the acini and the alveoli. University of Iowa

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Metabolic MAGIC

, 26 August 2020/in E-News /by 3wmedia

Researchers have identified 38 new genetic regions that are associated with glucose and insulin levels in the blood. This brings the total number of genetic regions associated with glucose and insulin levels to 53, over half of which are associated with type 2 diabetes.
The researchers used a technology that is 100 times more powerful than previous techniques used to follow-up on genome-wide association results. This technology, Metabochip, was designed as a cost-effective way to find and map genomic regions for a range of cardiovascular and metabolic characteristics on a large scale. Previous approaches were not cost effective and tested only 30-40 DNA sequence variations, but this chip allowed researchers to look at up to 200,000 DNA sequence variations for many different traits at one time. The team hoped to find new variants influencing blood glucose and insulin traits and to identify pathways involved in the regulation of insulin and glucose levels.
‘We wanted to use this improved Metabochip technology to see whether we could find additional genomic associations that may have been previously missed,’ says Dr Claudia Langenberg, co-lead author from the Medical Research Council Epidemiology Unit, Cambridge. ‘Our earlier work identified 23 genetic regions associated with blood glucose levels, highlighting important biological pathways involved in the regulation of glucose. At that stage, and before the design of the Metabochip, we were still limited by our capacity to quickly follow-up and afford parallel genotyping of promising, but unconfirmed genetic regions associated with glucose levels in many different studies across the world.’
The team combined data from new samples typed on the Metabochip with data from a previous study to discover genetic regions associated with blood glucose and insulin levels. They identified 38 previously unknown regions for three different quantitative traits associated with blood glucose levels; fasting glucose concentrations, fasting insulin concentrations and post-challenge glucose concentrations.
.’ Further analysis such as genetic mapping or ‘fine-mapping’ and functional analysis will expand and improve our understanding of the control of glucose and insulin levels in healthy persons and what goes wrong in type 2 diabetes patients. ‘
…’Our research is beginning to allow us to look at the overlap between genomic regions that influence insulin levels and other metabolic traits,’ says Dr Inga Prokopenko, co-lead author from the University of Oxford. ‘We observed some overlap between the regions we identified and genetic regions associated with abdominal obesity and various lipid levels, which are a hallmark of insulin resistance. We hope that these studies will help to find gene networks with potential key modifiers for important metabolic processes and related diseases, such as type 2 diabetes.’
The team also found many more, less significant, genetic regions that may be associated with blood glucose and insulin levels but currently don’t have the available data to definitively establish them as genome-wide significant. This supports previous evidence that there is a long tail of many other genetic regions that add up to quite small genetic effects but may increase the risk of such diseases as diabetes. Collectively, these less significant associations may represent important blood glucose and insulin level associations.
‘In addition to these top signals there is statistical evidence that many other regions that appear to be biologically plausible also influence these traits, but what’s limiting is that we don’t have large enough sample sizes to have the power to validate them,’ explains Dr Inês Barroso, co-lead author from the Wellcome Trust Sanger Institute. ‘Nevertheless, studying these functionally would be extremely beneficial if we want to fully understand the biology of blood glucose levels and the origin of diabetes.’
‘What we’ve found in this study is a number of genomic regions that influence blood glucose and insulin traits. Further analysis such as genetic mapping or ‘fine-mapping’ and functional analysis will expand and improve our understanding of the control of glucose and insulin levels in healthy persons and what goes wrong in type 2 diabetes patients.’ Wellcome Trust Sanger Institute

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Evaluation of rapid influenza virus tests

, 26 August 2020/in E-News /by 3wmedia

A fast, accurate diagnosis is essential for efficient treatment, especially in patients with complications. The Rapid Influenza Diagnostic Tests (RIDTs) for influenza detection have been developed to subtype the influenza virus, but rapid testing is no good unless it is accompanied by high levels of selectivity, specificity and accuracy. Over the course of a year, this study obtained over 1,000 nasal aspirate samples from patients with symptoms of influenza-like illness and evaluated by 2 types of RIDTs, Standard Diagnosis (SD) and QuickVue (QV) Rapid tests followed by real-time RT-PCR. The results showed that the SD rapid test appeared to be more sensitive than the QV test during high season activity, whereas the QV test was more sensitive during the period of low influenza virus activity. The conclusion was that due to persistent genetic drift of the influenza virus, the available RIDTs should be re-evaluated each year.

Makkoch J. et al. Clin. Lab. 2012; 58(9-10): 905-910. DOI: 10.7754/Clin.Lab.2011.111003

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Could poor sleep contribute to symptoms of schizophrenia?

, 26 August 2020/in E-News /by 3wmedia

Neuroscientists studying the link between poor sleep and schizophrenia have found that irregular sleep patterns and desynchronised brain activity during sleep could trigger some of the disease’s symptoms. The findings suggest that these prolonged disturbances might be a cause and not just a consequence of the disorder’s debilitating effects.
The possible link between poor sleep and schizophrenia prompted the research team, led by scientists from the University of Bristol, the Lilly Centre for Cognitive Neuroscience and funded by the Medical Research Council (MRC), to explore the impact of irregular sleep patterns on the brain by recording electrical brain activity in multiple brain regions during sleep.
For many people, sleep deprivation can affect mood, concentration and stress levels. In extreme cases, prolonged sleep deprivation can induce hallucinations, memory loss and confusion all of which are also symptoms associated with schizophrenia.
Dr Ullrich Bartsch, one of the study’s researchers, said: ‘Sleep disturbances are well-documented in the disease, though often regarded as side effects and poorly understood in terms of their potential to actually trigger its symptoms.’
Using a rat model of the disease, the team’s recordings showed de-synchronisation of the waves of activity which normally travel from the front to the back of the brain during deep sleep. In particular the information flow between the hippocampus — involved in memory formation, and the frontal cortex — involved in decision-making, appeared to be disrupted. The team’s findings reported distinct irregular sleep patterns very similar to those observed in schizophrenia patients.
Dr Matt Jones, the lead researcher from the University’s School of Physiology and Pharmacology, added: ‘Decoupling of brain regions involved in memory formation and decision-making during wakefulness are already implicated in schizophrenia, but de-coupling during sleep provides a new mechanistic explanation for the cognitive deficits observed in both the animal model and patients: sleep disturbances might be a cause, not just a consequence of schizophrenia. In fact, abnormal sleep patterns may trigger abnormal brain activity in a range of conditions.’
Cognitive deficits — reduced short term memory and attention span, are typically resistant to medication in patients. The findings from this study provide new angles for neurocognitive therapy in schizophrenia and related psychiatric diseases. Bristol University

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Back to the future in the war against tuberculosis?

, 26 August 2020/in E-News /by 3wmedia

Vitamin D, best known for its role in calcium uptake and bone density has also been shown to have beneficial effects on the immune system, with some studies demonstrating a correlation between higher vitamin D intake and a lower incidence of cancer, and that adequate vitamin D levels may also decrease the risk of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Now, a recent study, conducted by doctors across London hospitals and published in the Proceedings of the National Academy of Sciences, has shown that tuberculosis (TB) patients recovered more quickly when given both the vitamin and antibiotics. This idea is reminiscent of earlier times when TB patients, in the days before antibiotics, were prescribed sunbathing, which increases vitamin D production. This study found that recovery was almost two weeks faster when vitamin D was added to the treatment regime, with patients clearing the infection in 23 days on average, compared to 36 days for patients given antibiotics and a placebo. Vitamin D treatment will not replace antibiotics, but might well become a useful extra weapon, particularly with the increasing prevalence of drug-resistant TB. The vitamin seems to work by reducing the inflammatory response to the infection and helping the lungs to heal more quickly. If these lung cavities heal more quickly, patients are infectious for a shorter period of time and may also suffer less lung damage. Stronger evidence and trials to find the best dose and form of vitamin D will be needed before the treatment is put into widespread use.

http://www.pnas.org/

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Severe flu increases risk of Parkinson’s: UBC research

, 26 August 2020/in E-News /by 3wmedia

Severe influenza doubles the odds that a person will develop Parkinson’s disease later in life, according to University of British Columbia researchers.
However, the opposite is true for people who contracted a typical case of red measles as children – they are 35 per cent less likely to develop Parkinson’s, a nervous system disorder marked by slowness of movement, shaking, stiffness, and in the later stages, loss of balance.
The findings by researchers at UBC’s School of Population and Public Health and the Pacific Parkinson’s Research Centre are based on interviews with 403 Parkinson’s patients and 405 healthy people in British Columbia, Canada.
Lead author Anne Harris also examined whether occupational exposure to vibrations – such as operating construction equipment – had any effect on the risk of Parkinson’s. In another study she and her collaborators reported that occupational exposure actually decreased the risk of developing the disease by 33 percent, compared to people whose jobs involved no exposure.
Meanwhile, Harris found that those exposed to high-intensity vibrations – for example, by driving snowmobiles, military tanks or high-speed boats – had a consistently higher risk of developing Parkinson’s than people whose jobs involved lower-intensity vibrations (for example, operating road vehicles). The elevated risk fell short of the statistical significance typically used to establish a correlation, but was strong and consistent enough to suggest an avenue for further study, Harris says.
‘There are no cures or prevention programs for Parkinson’s, in part because we still don’t understand what triggers it in some people and not others,’ says Harris, who conducted the research while earning her doctorate at UBC. ‘This kind of painstaking epidemiological detective work is crucial in identifying the mechanisms that might be at work, allowing the development of effective prevention strategies.’ University of British Columbia

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Scientists developing quick way to ID people exposed to ionising radiation

, 26 August 2020/in E-News /by 3wmedia

There’s a reason emergency personnel train for the aftermath of a dirty bomb or an explosion at a nuclear power plant. They’ll be faced with a deluge of urgent tasks, such as identifying who’s been irradiated, who has an injury-induced infection, and who’s suffering from both.
Unfortunately, there isn’t a quick way to screen for people exposed to dangerous levels of radiation. There also isn’t a quick way to distinguish between people suffering from radiation exposure versus an infection due to an injury or chemical exposure.
The most common way to measure exposure is a blood assay that tracks chromosomal changes. Another approach is to watch for the onset of physical symptoms. But these methods can take several days to provide results, which is far too late to identify people who’d benefit from immediate treatment.
A much faster way could be coming. Research conducted by scientists from the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) could lead to a blood test that detects if a person has been exposed to radiation, measures their dose, and separates people suffering from inflammation injuries—all in a matter of hours.
The scientists identified eight DNA-repair genes in human blood whose expression responses change more than twofold soon after blood is exposed to radiation. They also learned how these genes respond when blood is exposed to inflammation stress, which can occur because of an injury or infection. Inflammation can mimic the effects of radiation and lead to false diagnoses.
The result is a panel of biochemical markers that can discriminate between blood samples exposed to radiation, inflammation, or both. The scientists believe these markers could be incorporated into a blood test that quickly triages people involved in radiation-related incidents.
‘In an emergency involving radiation exposure, it’s likely that only a small fraction of all possibly exposed people will be exposed to high doses that require immediate medical attention,’ says Andy Wyrobek of Berkeley Lab’s Life Sciences Division. ‘The goal is to quickly screen for these people so they can get treatment, and avoid overwhelming medical facilities with the larger number of people exposed to low levels of radiation with no immediate medical needs. Our research could lead to a blood test that enables this.’
Wyrobek conducted the research with fellow Berkeley Lab scientists Helen Budworth and Antoine Snijders, as well as several other scientists from Berkeley Lab and other institutions.
Because DNA is one of the major targets of radiation, the Berkeley Lab scientists began their research by focusing on 40 genes that regulate the expression of proteins that carry out DNA-repair tasks. They studied these genes in blood samples taken from healthy people before and after exposing the samples to 2 Gray of X-rays per year, which is about the radiation dose received by radiotherapy patients. They found twelve genes that underwent more than a twofold change in response after exposure. From these, they isolated eight genes that had no overlap between unirradiated and irradiated samples.
The scientists also treated the blood samples with a compound that mimics inflammatory stress. This enabled them to account for gene-expression responses that could be mistaken for signs of radiation exposure, but which are actually caused by injury or infection. In addition, they irradiated a portion of these samples to learn how the genes respond to both inflammation and radiation.
To validate their findings, the scientists analysed a separate dataset of blood samples that had also been irradiated. They found a close match between their own data and the independent dataset in how the eight genes respond after radiation exposure.
They also compared their findings to a large group of bone marrow transplant patients who received total-body radiation. Again, they found a close match between their data and the gene-expression responses of the patients after they received treatment.
More work is needed, but Wyrobek envisions a blood test using their biochemical markers could be administered via a handheld device similar to what diabetes patients use to check their blood sugar. The test could help emergency personnel quickly identify people exposed to high radiation doses who need immediate care, and people exposed to lower doses who only need long-term monitoring. Lawrence Berkeley National Laboratory

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Drop in testosterone tied to prostate cancer recurrence

, 26 August 2020/in E-News /by 3wmedia

Men whose testosterone drops following radiation therapy for prostate cancer are more likely to experience a change in PSA levels that signals their cancer has returned, according to new research from Fox Chase Cancer Center.
Specifically, men whose testosterone fell following various forms of radiation therapy were more likely to experience an increase in prostate-specific antigen (PSA)—often the first indication the cancer has recurred.
‘The men who had a decrease in testosterone also appear to be the men more likely to see an increase in PSA after treatment,’ says study author Jeffrey Martin, MD, resident physician in the Department of Radiation Oncology at Fox Chase.
In theory, doctors may one day be able to use testosterone levels to guide treatment decisions, says Martin. ‘For men with a decrease in testosterone, doctors might intervene earlier with other medications, or follow their PSA more closely than they would otherwise, to spot recurrences at an earlier time.’
Martin and his colleagues decided to conduct the study because there is limited information regarding testosterone levels after radiation treatment and what it means for prognosis. To investigate whether a decrease in testosterone has any clinical effects, Martin and his colleagues reviewed medical records from nearly 260 men who received radiation therapy for prostate cancer between 2002 and 2008. The men were treated with either brachytherapy, in which doctors insert radioactive seeds in the prostate, or intensity modulated radiation therapy (IMRT), in which an external beam of radiation is directed at the prostate.
The researchers found that testosterone levels tended to decrease following both forms of radiation therapy. And men who experienced a post-radiation drop in testosterone— particularly a significant drop—were more likely to see their PSA levels rise during the follow-up period.
Still, an increase in PSA—known as biochemical failure—was relatively rare, the authors found. ‘Only 4% of patients with low-risk prostate cancer had biochemical failure at five years,’ says Martin.
Even though researchers have seen testosterone decrease following another form of radiation, these latest findings are still somewhat surprising, says Martin, because testosterone is believed to drive prostate cancer. In fact, some patients with advanced forms are prescribed hormone therapy that attempts to knock down testosterone.
‘Seeing that a drop in testosterone is tied to recurrence is kind of a surprising result,’ says Martin. ‘We don’t necessarily know what this means yet. I think the relationship between testosterone levels following radiation therapy and prognosis needs more study, and until then it’s premature to say this is something patients should ask their doctors about.’
This was a small study that needs to be validated in a larger group of men before doctors begin basing their predictions of recurrence on patients’ testosterone levels, he cautions. ‘I think the link between testosterone and PSA needs more study, in a larger set of patients.’ EurekAlert

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Internet addiction – causes at the molecular level

, 26 August 2020/in E-News /by 3wmedia

Everybody is talking about Internet addiction – many people spend hours online and immediately start feeling bad if they are unable to do so. Medically, this phenomenon has not yet been as clearly described as nicotine or alcohol dependency. But a study conducted by researchers from the University of Bonn and the Central Institute of Mental Health (ZI) in Mannheim now provides indications that there are molecular-genetic connections in Internet addiction, too.
‘It was shown that Internet addiction is not a figment of our imagination,’ says the lead author, Privatdozent Dr. Christian Montag from the Department for Differential and Biological Psychology at the University of Bonn. ‘Researchers and therapists are increasingly closing in on it.’ Over the past years, the Bonn researchers have interviewed a total of 843 people about their Internet habits. An analysis of the questionnaires shows that 132 men and women in this group exhibit problematic behaviour in how they handle the online medium; all their thoughts revolve around the Internet during the day, and they feel their wellbeing is severely impacted if they have to go without it.
The researchers from the University of Bonn and the Central Institute of Mental Health in Mannheim compared the genetic makeup of the problematic Internet users with that of healthy control individuals. This showed that the 132 subjects are more often carriers of a genetic variation that also plays a major role in nicotine addiction. ‘What we already know about the nicotinic acetylcholine receptor in the brain is that a mutation on the related gene promotes addictive behavior,’ explains Dr. Montag. Nicotine from tobacco fits – just like acetylcholine, which is produced by the body – like a key into this receptor. Both these neurotransmitters play a significant role in activating the brain’s reward system. ‘It seems that this connection is not only essential for nicotine addiction, but also for Internet addiction,’ reports the Bonn psychologist.
The actual mutation is on the CHRNA4 gene that changes the genetic makeup for the Alpha 4 subunit on the nicotinic acetylcholine receptor. ‘Within the group of subjects exhibiting problematic Internet behaviour this variant occurs more frequently – in particular, in women,’ says Dr. Montag. This finding will have to be validated further because numerous surveys have found that men are more prone to Internet addiction than women. The psychologist assumes, ‘The sex-specific genetic finding may result from a specific subgroup of Internet dependency, such as the use of social networks or such.’
Dr. Montag added that studies including more subjects are required to further analyse the connection between this mutation and Internet addiction. ‘But the current data already shows that there are clear indications for genetic causes of Internet addiction.’ He added that with the mutation, a biological marker had been found that would allow to characterise online addiction from a neuro-scientific angle. ‘If such connections are better understood, this will also result in important indications for better therapies,’ says Dr. Montag. University Bonn

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‘Promising results’ for bowel cancer breath-test

, 26 August 2020/in E-News /by 3wmedia

Scientists say they have developed a breath-test that can accurately tell if a person has bowel cancer. The test, which looks for exhaled chemicals linked to tumour activity, was able to identify a majority of patients with the disease.
The British Journal of Surgery reported an overall accuracy of 76%.
However, another scientist said it was unlikely a fully functioning and reliable breath-test would be available soon for the general public. Scientists are working on breath-tests for a host of other diseases, including several types of cancer, TB and diabetes.
If diagnosed and treated early, the chances of stopping cancer can be good, but there is often little or no outward sign of the disease until it has progressed significantly.
The current screening test for bowel cancer looks for signs of blood in the faeces, but only a small proportion of those who test positive actually have colorectal cancer, which means unnecessary and invasive further testing for many people.
The breath-test technology relies on the idea that the biology of tumours can lead to the production of specific ‘volatile organic compounds’, combinations of chemicals unlikely in a healthy person.
These can be found in small amounts in the breath of the patient, and early studies found dogs could be trained to identify them – although the latest study relies an electronic device to analyse breath gases.
The team from a hospital in Bari, southern Italy, compared the breath of 37 patients known to have bowel cancer with that of 41 ‘controls’ who were thought to be healthy.
The initial test identified the cancer patients with 85% accuracy, and although, when combined with a follow-up test, the overall result fell to 76%, the researchers were upbeat about its potential.
‘The present findings further support the value of breath-testing as a screening tool,’ they say.
It might be possible that the technique could help identify patients whose cancer was returning after treatment.
Bigger studies with a greater number of patients were now needed to fine-tune the test and confirm it worked, said Dr Donato Altomare and colleagues. BBC

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