KigaliHealth.com - Page 4 of 35 - Health and Medical Info in Kigali

Scientists edit human embryos to safely remove disease for the first time – here’s how they did it

Human eight cell embryo for IVF selection.
K. Hardy, Wellcome Images , CC BY-SA

Joyce Harper, UCL and Helen O’Neill, UCL

Scientists in the US have released a paper showing that they have successfully edited human embryos to correct a mutation that causes an inheritable heart condition. The findings are hugely important as they demonstrate for the first time that the technology may one day be used safely to edit out many devastating diseases.

But how close to curing genetic diseases does the new study actually take us? And how concerned should we be about the ethical implications of the technology?

The genome editing tool used, CRISPR-Cas9, has transformed the field of biology in the short time since its discovery in that it not only promises, but delivers. CRISPR has surpassed all previous efforts to engineer cells and alter genomes at a fraction of the time and cost.

The technology, which works like molecular scissors to cut and paste DNA, is a natural defence system that bacteria use to fend off harmful infections. This system has the ability to recognise invading virus DNA, cut it and integrate this cut sequence into its own genome – allowing the bacterium to render itself immune to future infections of viruses with similar DNA. It is this ability to recognise and cut DNA that has allowed scientists to use it to target and edit specific DNA regions.

When this technology is applied to “germ cells” – the sperm and eggs – or embryos, it changes the germline. That means that any alterations made would be permanent and passed down to future generations. This makes it more ethically complex, but there are strict regulations around human germline genome editing, which is predominantly illegal. The UK received a licence in 2016 to carry out CRISPR on human embryos for research into early development. But edited embryos are not allowed to be inserted into the uterus and develop into a fetus in any country.

GM babies are a long way off.
Stockce/Shutterstock

Germline genome editing came into the global spotlight when Chinese scientists announced in 2015 that they had used CRISPR to edit non-viable human embryos – cells that could never result in a live birth. They did this to modify the gene responsible for the blood disorder β-thalassaemia. While it was met with some success, it received a lot of criticism because of the premature use of this technology in human embryos. The results showed a high number of potentially dangerous, off-target mutations created in the procedure.

Impressive results

The new study, published in Nature, is different because it deals with viable human embryos and shows that the genome editing can be carried out safely – without creating harmful mutations. The team used CRISPR to correct a mutation in the gene MYBPC3, which accounts for approximately 40% of the myocardial disease hypertrophic cardiomyopathy. This is a dominant disease, so an affected individual only needs one abnormal copy of the gene to be affected.

The researchers used sperm from a patient carrying one copy of the MYBPC3 mutation to create 54 embryos. They edited them using CRISPR-Cas9 to correct the mutation. Without genome editing, approximately 50% of the embryos would carry the patients’ normal gene and 50% would carry his abnormal gene.

After genome editing, the aim would be for 100% of embryos to be normal. In the first round of the experiments, they found that 66.7% of embryos – 36 out of 54 – were normal after being injected with CRIPSR. Of the remaining 18 embryos, five had remained unchanged, suggesting editing had not worked. In 13 embryos, only a portion of cells had been edited.

The level of efficiency is affected by the type of CRISPR machinery used and, critically, the timing in which it is put into the embryo. The researchers therefore also tried injecting the sperm and the CRISPR-Cas9 complex into the egg at the same time, which resulted in more promising results. This was done for 75 mature donated human eggs using a common IVF technique called intracytoplasmic sperm injection. This time, impressively, 72.4% of embryos were normal as a result. The approach also lowered the number of embryos containing a mixture of edited and unedited cells (these embryos are called mosaics).

Embryos were created with the sperm of a patient.
Sebastian Kaulitzk/Shutterstock

Finally, the team injected a further 22 embryos which were grown into blastocyst – a later stage of embryo development. These were sequenced and the researchers found that the editing had indeed worked. Importantly, they could show that the level of off-target mutations was low.

A brave new world?

So does this mean we finally have a cure for debilitating, heritable diseases? It’s important to remember that the study did not achieve a 100% success rate. Even the researchers themselves stress that further research is needed in order to fully understand the potential and limitations of the technique.

In our view, it is unlikely that genome editing would be used to treat the majority of inherited conditions anytime soon. We still can’t be sure how a child with a genetically altered genome will develop over a lifetime, so it seems unlikely that couples carrying a genetic disease would embark on gene editing rather than undergoing already available tests – such as preimplantation genetic diagnosis or prenatal diagnosis – where the embryos or fetus are tested for genetic faults.

Many people worry about where the line will be drawn between altering and ameliorating human embryos. If there is a risk that a person will have short stature because of an abnormality of growth hormone, would editing their genome to make them taller be considered a treatment or an enhancement? It is easy to see how the line could get blurred.

Most countries are debating the clinical, ethical and social significance of being able to genetically modify human embryos. It may be that some countries will never permit germline genome editing because of moral and ethical concerns. And even if the law in the UK was changed to allow genome editing, it would be highly regulated by the Human Fertilisation and Embryology Authority to ensure it is only used for medical reasons.

That doesn’t mean that we shouldn’t have a public debate about the ethical implications – it is hugely important that we do. But it is important to remember to celebrate the amazing advances of this field of research, which could one day help eradicate many devastating diseases, before jumping to conclusions about a brave new world.

Joyce Harper, Professor of Human Genetics and Embryology, UCL and Helen O’Neill, Program Director of Reproductive Science and Women’s Health MSc, UCL

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Should we edit the genomes of human embryos? A geneticist and social scientist discuss

Sirtravelalot/Shutterstock.com

Felicity Boardman, University of Warwick and Helen O’Neill, UCL

This is an article from Head to Head, a series in which academics from different disciplines chew over current debates. Let us know what else you’d like covered – all questions welcome. Details of how to contact us are at the end of the article.

Felicity Boardman: The birth of a child with genetic disease is generally an unexpected event. The parents of these children typically won’t have a family history with the condition, or even be aware that they are genetic “carriers”: that they can transmit a genetic condition to their offspring, but do not have it themselves. Indeed, there are currently only two carrier screening programmes active in the UK that are implemented during pregnancy (one for for thalassaemia, and the other for sickle cell trait). So for most parents, discovering the condition in their family occurs through their child’s diagnosis, either through the newborn heel prick test, or following the onset of symptoms.

Even in cases where a genetic condition in the foetus is identified during pregnancy, the options for would-be parents remain extremely limited. Many of the most common genetic conditions still lack effective treatments or cures. This means that, for many parents, the information leads to a decision about whether or not to terminate the pregnancy, or continue in the knowledge that the child will have the condition.

Sickled red blood cells in liver tissue.
SB Lucas/Wellcome Collection, CC BY

The introduction of genome editing, however, signals a dramatic departure from this usual pathway through reproductive care. Although the foundations of genome editing were laid initially in the 1960s when proteins were first used to “cut” DNA, the recent development of new techniques and technologies (such as CRISPR-Cas9) has made genome editing more precise, more cost-effective and consequently more accessible than ever before.

By intervening before a child is even born, the use of genome editing in human reproduction has the potential to alleviate some of the complicated and painful decisions around pregnancy termination – by providing a reproductive option that has, up until now, not been possible. That is, the possibility of removing the disease-causing genetic variant, while simultaneously preserving the life of the foetus.

Helen O’Neill: Genome editing indeed marks a significant shift, and not only in the area of reproduction, but also in the direction of tailored treatments and personalised medicine. It offers hope to those who, before now, have not had any better options than prescriptions and palliative care.

It’s an incredibly exciting time for such research both in terms of discovery and diagnostics. The advent of CRISPR genome editing has catapulted previous efforts in genomics and is being adopted globally. My research, for example, uses CRISPR genome editing to assess the treatment and understanding of sex chromosome disorders and neuromuscular disorders. There are two ways in which genome editing could be used for both treatment and prevention: somatic cell therapy, which could be used in newborns and adults, and germline genome editing, which would be used in an early embryo to prevent a disorder. In this second type, genome editing would aim to alter every cell of a resulting baby, and therefore these changes would be passed on to future generations, meaning that disease causing variants would be prevented from being passed on.

CRISPR-Cas9 allows scientists to target and activate or silence specific genes.
Vrx/Shutterstock.com

The use of genetic technologies in reproduction is frequently criticised for harbouring eugenic undertones. But genetic selection occurs with or without these technologies. For example, we make decisions about the genetics of our future offspring when we choose our mate. We make decisions about the health of our future offspring when we take supplements such as folic acid and improve our diet during pregnancy. Decades of research have yielded ever-increasing information about how we can protect and nurture our embryos, not only by including essential macronutrients but also by excluding harmful exposures such as alcohol and tobacco. We don’t ignore these welfare warnings. Nor is it considered elitist to adhere to them by choice to deliver a healthy baby.

But when comparing these genetic prompts to more purposeful permutations of our genetics using gene editing technology, the rationalisation for wanting a healthy baby somehow becomes displaced with irrational ideas about the creation of a “perfect” baby.

It is true that advances in research rarely lend themselves so quickly to clinical adoption. But safety is obviously the number one prerequisite for any research development to become medical practice. Proceeding with such medical advances will always be subject to rigorous oversight. So for many, genome editing – and the era of personalised medicine – is not something to be feared but embraced.

Mistrust and myth

FB: While caution is a good thing, fear of the technologies can make meaningful and progressive debate quite difficult. The association of genome editing with “designer babies”, for example, although making for catchy headlines, masks the intended uses of the technologies. The connotations of frivolity, commercialism and superficial decision making that comes with the term “designer” does a great disservice to the parents in these difficult situations who are facing complex and often deeply painful decisions.

HON: Yes: the term “designer” suggests that there is an element of choice and privilege to a baby that may be born with an edited genome. In fact, the opposite is more likely to be true; people will not edit the genomes of their embryos out of choice, but because they have no choice if they are to deliver a healthy, viable baby.

And as it stands, we are still debating the number of genes in the human genome and certainly do not know what all of the genes do. Even if we did, the unpredictability in the mechanism of genetic crossover between parental genomes precludes any realistic control or prediction of the majority of traits. Choosing partners based on what we see on the outside is a far more reliable method for designing our babies’ appearance.

All babies are ‘designed’ to some extent when we choose a partner.
Jacob Lund/Shutterstock.com

There is no doubt that a subject like this needs widespread discussion and debate and in fact recent surveys show that the public are optimistic about genome editing for curing diseases, but there can also be a lack of trust about the intended use of this technology. The distraction from the good that this technology can do is frustrating as a researcher. We should not extrapolate the worst possible outcome which encourages unrealistic and disingenuous ideas focusing on dystopian scenarios.

FB: I think some of this mistrust stems from fear of the unknown and a concern that this technology stands to alter not only our biology, but also our society. People with genetic disabilities, for example, those with spinal muscular atrophy, haemophilia and cystic fibrosis (who I work with during my research), are set to be impacted by the consequences of genome editing, yet they are not always included in stakeholder debates as much as they could be. This is in spite of the fact that people with disabilities have much to contribute to our understanding of what life with genetic disease is really like. Insights that are highly relevant to decisions about which conditions are suitable candidates for genome editing.

HON: But the use of genome editing can also be seen as addressing some of the objections to prenatal testing and pregnancy termination raised by disability rights supporters. By treating the foetus’ or embyro’s condition, rather than terminating them, genome editing may be an attractive alternative for those who disagree with pregnancy termination or embryo disposal on the grounds of disability or otherwise.

Separation of DNA fragments.
Guy Tear/Wellcome Collection, CC BY

What’s at stake?

FB: That’s of course true, but for some, this development is regarded as coming at a cost. Genome editing not only changes the genome of the embryo it treats, but also that of every generation that comes after it, and so critical questions still remain about how and when it would be ethically and socially appropriate to implement it. Indeed, it has been suggested that over time, genome editing could effectively remove particular disease-causing traits from the human gene pool.

While this may seem a positive development to many people, the question of which conditions and traits genome editing should be used to treat, and which it should not, is far from straightforward. Research I have conducted with families living with a range of conditions that could all one day be candidate conditions for genome editing, for example, has revealed that a person’s relationship to their genetic condition is often complex. For some, their disability is an integral and valued part of their identity, while for others, an unwelcome burden. As such, ascertaining the quality of life of a person with a genetic disorder (particularly before birth) is a near impossible task.

As genome editing technologies move into mainstream healthcare and become widely adopted, it is possible that would-be parents will feel under pressure to use them. This is a concern that has long been raised in relation to informed consent and antenatal screening for Down’s Syndrome. The potential stigmatisation and branding of parents who forgo the technologies as “selfish” or “irresponsible” needs to be seriously considered, as well as the possibility that this stigma could extend to the disabled people already living with “editable” conditions (the numbers of whom are likely to reduce over time).

Indeed, the public profile of these (often rare) genetic conditions will shift and alter through the use of genome editing – from conditions once considered “chance” occurrences, to preventable diseases. This change is likely to have social consequences, as well as biological ones.

Fibrous deposits in pancreas due to cystic fibrosis.
Anne Clark, University of Oxford/Wellcome Collection, CC BY

HON: It is essential to put genome editing in context with what is already available in terms of screening and pre-implantation genetic diagnosis – which has been available for 30 years. With this, every single condition needs to be appraised and legally approved before it can be tested for. And ultimately, the decision comes from the parents.

It is also important to remember that we cannot predict the pattern of genetics or the heritability of disorders. So suggesting that conditions would be “eliminated” is certainly not the goal of researchers, nor is it realistic. Not all genetic disorders are inherited from the family line, many are sporadic or “de novo” mutations which occur through chance. While germline genome editing certainly has consequences for future generations, many current standard treatments are not ideal and have unwanted side effects, but they are the best we currently have. Take for example cancer radiation therapy, which not only alters, but destroys, the germline.

More research is critical. We know less about the early developmental stages of a human embryo than we do of mice, worms, flies and fish. Knowledge is the most powerful prescription you can give, but it comes with a burden. It is important that with each new discovery we are able to fully consolidate our knowledge before advancing to the next level in research.

FB: I agree – and also think it’s important to note that we need more research that explores the technologies from a range of vantage points. Currently, there is a lack of dialogue between the various disciplines working in this area, including geneticists, scientists, bioethicists, sociologists and disability studies scholars. By removing some of the disciplinary divisions, we may better be able to see the full consequences of the technologies for everyone whose lives will be affected by them, the list of which seems to be ever-expanding.

If there’s a specific topic or question you’d like experts from different disciplines to discuss, you can:

* Email your question to josephine.lethbridge@theconversation.com

* Tell us on Twitter by tagging @ConversationUK with the hashtag #HeadtoHead, or

* Message us on Facebook.

Felicity Boardman, Assistant Professor in Social Science and Systems in Health, University of Warwick and Helen O’Neill, Lecturer in Reproductive and Molecular Genetics, UCL

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Just because you’re thin, doesn’t mean you’re healthy

Being thin doesn’t mean you can eat unhealthy foods and get away with it.
from www.shutterstock.com

Dominic Tran, University of Sydney

According to the Australian Institute of Health and Welfare, 63% of Australian adults are overweight or obese.

But it’s much harder to estimate how many are within a healthy weight range but have poor diets or sedentary lifestyles. These can cause significant health problems that will often be missed because the person appears to look “healthy”.

How do we judge the health of weight?

Obesity statistics often take estimates of body fat using body mass index (BMI). Although BMI isn’t perfectly correlated with body fat percentage, it’s a quick and easy method for collecting data using just the person’s height and weight. If the BMI is higher than 25, a person is considered “overweight”. If it’s above 30, they’re considered “obese”. But BMI doesn’t tell us how healthy someone is on the inside.

Using additional lifestyle measures, such as diet and exercise frequency over the last year, a recent report from the Queensland Health department estimated 23% of those who are not currently overweight or obese are at risk of being so in the future.

These figures indicate that the percentage of unhealthy-weight individuals does not accurately capture the percentage of unhealthy-lifestyle individuals, with the latter number likely to be much higher.

If you’re not overweight, does a healthy lifestyle matter?

Many people think if they’re able to stay lean while eating poorly and not exercising, then that’s OK. But though you might appear healthy on the outside, you could have the same health concerns as overweight and obese individuals on the inside.

When considering risk factors associated with heart disease and stroke or cancer, we often think about health indicators such as smoking, cholesterol, blood pressure, and body weight. But poor diet and physical inactivity also each increase the risk for heart disease and have a role to play in the development of some cancers.

So even if you don’t smoke and you’re not overweight, being inactive and eating badly increases your risk of developing heart disease.

Little research has been done to compare the risk diet and exercise contributes to the development of heart disease in overweight versus skinny but unhealthy individuals. However, one study measured the risk of different lifestyle factors associated with complications following acute coronary syndrome – a sudden reduction in blood flow to the heart.

It found adherence to a healthy diet and exercise regime halved the risk of having a major complication (such as stroke or death) in the six months following the initial incident compared with non-adherence.

Unhealthy diets are bad for your body, but what about your brain?

Recent research has also shown overconsumption of high-fat and high-sugar foods may have negative effects on your brain, causing learning and memory deficits. Studies have found obesity is associated with impairments in cognitive functioning, as assessed by a range of learning and memory tests, such as the ability to remember a list of words previously presented some minutes or hours earlier.

Notably, this relationship between body weight and cognitive functioning was present even after controlling for a range of factors including education level and existing medical conditions.

Of particular relevance to this discussion is the growing body of evidence that diet-induced cognitive impairments can emerge rapidly — within weeks or even days. For example, a study conducted at Oxford University found healthy adults assigned to a high-fat diet (75% of energy intake) for five days showed impaired attention, memory, and mood compared to a low-fat diet control group.

Another study conducted at Macquarie University also found eating a high-fat and high-sugar breakfast each day for as little as four days resulted in learning and memory deficits similar to those observed in overweight and obese individuals.

These findings confirm the results of rodent studies showing specific forms of memories can be impaired after only a few days on a diet containing sugar water and human “junk” foods such as cakes and biscuits.

Body weight was not hugely different between the groups eating a healthy diet and those on high fat and sugar diets. So this shows negative consequences of poor dietary intake can occur even when body weight has not noticeably changed. These studies show body weight is not always the best predictor of internal health.

We still don’t know much about the mechanism(s) through which these high-fat and high-sugar foods impair cognitive functioning over such short periods. One possible mechanism is the changes to blood glucose levels from eating high-fat and high-sugar foods. Fluctuations in blood glucose levels may impair glucose metabolism and insulin signalling in the brain.

Many people use low body weight to excuse unhealthy eating and physical inactivity. But body weight is not the best indicator of internal well-being. A much better indicator is your diet. When it comes to your health, it’s what’s on the inside that counts and you really are what you eat.

Dominic Tran, Postdoctoral Research Associate, University of Sydney

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Why do some people hurt more than others?

Some people feel more pain than others.
Mikhail_Kayl / Shutterstock.com

Erin Young, University of Connecticut

Anyone who came of age in the 1990s remembers the “Friends” episode where Phoebe and Rachel venture out to get tattoos. Spoiler alert: Rachel gets a tattoo and Phoebe ends up with a black ink dot because she couldn’t take the pain. This sitcom storyline is funny, but it also simply illustrates the question that I and many others in the field of “pain genetics” are trying to answer. What is it about Rachel that makes her different from Phoebe? And, more importantly, can we harness this difference to help the “Phoebes” of the world suffer less by making them more like the “Rachels”?

Are you a ‘Rachel’ or ‘Phoebe’ when it comes to pain?
AP Photo/Reed Saxon

Pain is the single most common symptom
reported when seeking medical attention. Under normal circumstances, pain signals injury, and the natural response is to protect ourselves until we have recovered and the pain subsides. Unfortunately, people differ not only in their ability to detect, tolerate and respond to pain but also in how they report it and how they respond to various treatments. This makes it difficult to know how to effectively treat each patient. So, why isn’t pain the same in everyone?

Individual differences in health outcomes often result from complex interactions of psychosocial, environmental and genetic factors. While pain may not register as a traditional disease like heart disease or diabetes, the same constellation of factors are at play. The painful experiences throughout our lifetime occur against a background of genes that make us more or less sensitive to pain. But our mental and physical state, previous experiences – painful, traumatic – and the environment can modulate our responses.

If we can better understand what makes individuals more or less sensitive to pain in all kinds of situations, then we are that much closer to reducing human suffering by developing targeted personalized pain treatments with lower risks of misuse, tolerance and abuse than the current treatments. Ultimately, this would mean knowing who is going to have more pain or need more pain-killing drugs, and then being able to effectively manage that pain so the patient is more comfortable and has a quicker recovery.

Not all pain genes are the same

The level of pain an individual senses, mild to excruciating, depends on the types of pain associated genes.
donskarpo / Shutterstock.com

With the sequencing of the human genome, we know a lot about the number and location of genes that make up our DNA code. Millions of small variations within those genes have also been identified, some that have known effects and some that don’t.

These variations can come in a number of forms, but the most common variation is the single nucleotide polymorphism – SNP, pronounced “snip” – representing a single difference in the individual units that make up DNA.

There are approximately 10 million known SNPs in the human genome; an individual’s combination of SNPs makes up his or her personal DNA code and differentiates it from that of others. When a SNP is common, it is referred to as a variant; when a SNP is rare, found in less than 1 percent of the population, then it is called a mutation. Rapidly expanding evidence implicates dozens of genes and variants in determining our pain sensitivity, how well analgesics – like opioids – reduce our pain and even our risk for developing chronic pain.

A history of pain tolerance

The first studies of “pain genetics” were of families with an extremely rare condition characterized by the absence of pain. The first report of congenital insensitivity to pain described “pure analgesia” in a performer working in a traveling show as “The Human Pincushion.” In the 1960s there were reports of genetically related families with children who were pain-tolerant.

Teacher’s aide Sue Price, right, examines Ashlyn Blocker’s head for scrapes, after she bumped it after school. Ashlyn never complains because the 5-year-old is among a small number of people in the world known to have congenital insensitivity to pain – a rare genetic disorder that makes her unable to feel pain.
AP Photo/Stephen Morton

At that time the technology did not exist to determine the cause of this disorder, but from these rare families we know that CIP – now known by wonkier names like Channelopathy-associated insensitivity to pain and Hereditary Sensory and Autonomic Neuropathy – is the result of specific mutations or deletions within single genes required for transmitting pain signals.

The most common culprit is one of a small number of SNPs within SCN9A, a gene that encodes a protein channel necessary for sending pain signals. This condition is rare; only a handful of cases have been documented in the United States. While it might seem like a blessing to live without pain, these families must be always on alert for severe injuries or fatal illnesses. Typically children fall down and cry, but, in this case, there’s no pain to differentiate between a scraped knee and a broken knee cap. Pain insensitivity means that there is no chest pain signaling a heart attack and no lower right abdominal pain hinting at appendicitis, so these can kill before anyone knows that there is something wrong.

Supersensitivity to pain

Variations within SCN9A not only cause pain insensitivity, but have also been shown to trigger two severe conditions characterized by extreme pain: primary erythermalgia and paroxysmal extreme pain disorder. In these cases, the mutations within SCN9A cause more pain signals than normal.

These types of heritable pain conditions are extremely rare and, arguably, these studies of profound genetic variations reveal little about more subtle variations that may contribute to individual differences in the normal population.

However, with the growing public acceptance of genome-based medicine and calls for more precise personalized health care strategies, researchers are translating these findings into personalized pain treatment protocols that match a patient’s genes.

Many of the answers to why pain sensitivity differs from person to person lies in our genes.
Sergei Drozd / Shutterstock.com

Do genetic variations affect pain in everyone?

We know some of the major genes that influence pain perception and new genes are being identified all the time.

The SCN9A gene is a major player in controlling the body’s response to pain by activating or silencing the sodium channel. But whether it amplifies or dampens pain depends on the mutation an individual carries.

Estimates suggest that up to 60 percent of the variability in pain is the result of inherited – that is, genetic – factors. Stated simply, this means that pain sensitivity runs in families through normal genetic inheritance, much like height, hair color or skin tone.

Turns out that SCN9A also plays a role in pain in the normal population. A relatively more common SNP within SCN9A, called 3312G>T which occurs in 5 percent of the population, has been shown to determine sensitivity to post-operative pain and how much opioid medication is needed to control it. Another SNP in SCN9A gene causes greater sensitivity for those with pain caused by osteoarthritis, lumbar disc removal surgery, amputee phantom limbs and pancreatitis.

New painkillers from sea creatures

Pufferlike, like *Arothron meleagris* can produce a toxin that works by blocking the transmission of pain signals.
NPS photo – Bill Eichenlaub

Therapeutically, we have been using local anesthetics, including lidocaine, to treat pain by inducing a short term block of the channel to stop pain transmission. These drugs have been continuously used to safely and effectively block pain for more than a century.

Interestingly, researchers are evaluating tetrodotoxin, a potent neurotoxin produced by sea creatures like pufferfish and octopuses, which works by blocking pain signal transmission, as a potential pain killer. They have shown early efficacy in treating cancer pain and migraine. These drugs and toxins induce the same state that is present in those with congenital insensitivity to pain.

If there’s one silver lining to the opioid crisis, it is the realization that we need more precise tools to treat pain – ones that treat pain at the source and come with fewer side effects and risk. By understanding the genetic contribution to pain sensitivity, susceptibility to chronic pain and even analgesic response, we can then design treatments that address the “why” of pain and not just the “”where.” We’re beginning to design precision pain management strategies already, and the benefit to humankind will only increase as we know more about why pain differs among people.

Erin Young, Assistant Professor, University of Connecticut School of Nursing; Assistant Director, UCONN Center for Advancement in Managing Pain, University of Connecticut

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Health Check: what happens when you hold in a fart?

Better out than in.
Sementsova Lesia/Shutterstock

Clare Collins, University of Newcastle

Ever been in a situation where passing wind is going to be hugely embarrassing and you’ve had to hold in a fart? Let’s face it – we all have.

Trying to hold it in leads to a build up of pressure and major discomfort. A build up of intestinal gas can trigger abdominal distension, with some gas reabsorbed into the circulation and exhaled in your breath. Holding on too long means the build up of intestinal gas will eventually escape via an uncontrollable fart.

The research is not clear on whether the rise in pressure in your rectum increases your chance of developing a condition called diverticulitis, where small pouches develop in the gut lining and become inflamed – or whether it doesn’t matter at all.

What is flatus?

Flatus, farts and breaking wind refer to intestinal gases that enter the rectum due to the body’s usual gastrointestinal processes of digestion and metabolism and then leave via the anus.

As your body digests food in the small intestine, components that can’t be broken down move further along the gastrointestinal track and eventually into the large intestine called the colon.

Intestinal bacteria break down some of the contents by fermentation. This process produces gases and by products called fatty acids that are reabsorbed and used in metabolic pathways related to immunity and preventing disease development.

Gases can either be reabsorbed through the gut wall into the circulation and eventually exhaled through the lungs or excreted via the rectum, as a fart.

How much flatus is normal?

It can be challenging for researchers to get people to sign up for experiments that measure farts. But thankfully, ten healthy adults volunteered to have the amount of gas they passed over a day quantified.

In a 24-hour period all the flatus they expelled was collected via a rectal catheter (ouch). They ate normally but to ensure a boost in gas production they also had to eat 200 grams (half a large can) of baked beans.

The participants produced a median total volume of 705ml of gas in 24 hours, but it ranged from 476ml to 1,490ml per person. Hydrogen gas was produced in the greatest volume (361ml over 24 hours), followed by carbon dioxide (68ml/24 hr). Only three adults produced methane, which ranged from 3ml/24 to 120ml/24 hr. The remaining gases, thought to mostly be nitrogen, contributed about 213ml/24 hr.

Men and women produced about the same amount of gas and averaged eight flatus episodes (individual or a series of farts) over 24 hours. The volume varied between 33 and 125 ml per fart, with bigger amounts of intestinal gas released in the hour after meals.

Gas was also produced while they were asleep, but at half the rate compared to during the day (median 16ml/hr vs 34ml/hr).

Fibre and flatus

In a study on dietary fibre and flatus, researches investigated what happens to intestinal gas production when you put people on a high-fibre diet.

The researchers got ten healthy adult volunteers to eat their usual diet for seven days while consuming 30 grams of psyllium a day as a source of soluble fibre, or not. In the psyllium week, they were asked to add 10 grams – about one heaped tablespoon – to each meal.

Not the best choice if you’ve been holding on.
By GoodStudio

At the end of each week, the participants were brought into the lab and, in a carefully controlled experiment, had an intra-rectal catheter inserted to quantify how gas (in terms of gas volume, pressure and number) moved through the intestine over a couple of hours.

They found the high psyllium-fibre diet led to longer initial retention of gas, but the volume stayed the same, meaning fewer but bigger farts.

Where do the gases come from?

Gas in the intestines comes from different sources. It can be from swallowing air. Or from carbon dioxide produced when stomach acid mixes with bicarbonate in the small intestine. Or gasses can be produced by bacteria that are located in the large intestine.

While these gases are thought to perform specific tasks that impact on health, producing excessive intestinal gas can cause bloating, pain, borborygmus (which means rumbling sounds), belching and lots of farts.

The smelliest farts are due to sulphur containing gases. This was confirmed in a study of 16 healthy adults who were fed pinto beans and lactulose, a non-absorbable carbohydrate that gets fermented in the colon. The odour intensity of flatus samples was evaluated by two judges (pity them).

The good news was that in a follow-up experiment, the researchers identified that a charcoal-lined cushion was able to help quash the smell of the sulphur gases.

Finally, some bad news for jet-setters: pressurised cabins on aeroplanes mean you’re more likely to pass flatus due to the gas volume expanding at the lower cabin pressure, compared to being on the ground. With modern noise-reduction features, your fellow passengers are more likely than they used to be to hear you fart.

What should you do?

The next time you feel a large volume of intestinal gas getting ready to do what it does, try to move to a more convenient location. Whether you make it there or not, the best thing for your digestive health is to just let it go.

For some creative ideas (and a chuckle) on how to hold in a fart, check this Wiki How to do anything.

Step 1: Clench your butt-cheeks.
Screen shot from wikihow.com

Clare Collins, Professor in Nutrition and Dietetics, University of Newcastle

This article is republished from The Conversation under a Creative Commons license. Read the original article.

What causes multiple sclerosis? What we know, don’t know and suspect

People exposed to low levels of sunlight are more likely to have MS than those who live in warm climates.
chuttersnap

Trevor Kilpatrick, Florey Institute of Neuroscience and Mental Health

US actress Selma Blair announced on the weekend she has been diagnosed with multiple sclerosis. “I have probably had this incurable disease for 15 years at least,” she wrote. “And I am relieved to at least know.”

Selma Blair shared the news on Instagram.
Instagram

Multiple sclerosis is an autoimmune disease, where the body mistakenly attacks the brain and spinal cord. It does this by damaging myelin – the protective coating around the nerves. When myelin is damaged, messages can no longer be clearly transmitted from the brain and spinal cord to other parts of the body.

The resulting symptoms include extreme tiredness, loss of concentration and memory, numbness, sensitivity to heat and cold, difficulties walking and balancing, spasms, dizziness and low mood.

Blair, aged 46, is one of 400,000 people in the United States with MS. The prevalence is similar to that in Australia, where around 25,000 people live with the disease. The average age of onset for MS is 30, and around three-quarters of those affected are women.

There’s still a lot we don’t know about the causes, but so far the research indicates our genes and environment each have a role in driving susceptibility to MS.

Genetics

Genetics plays an important role in the development of MS, with more than 200 genetic markers implicated in the disease. Collectively, the identified genes may account for up to 25% of the genetic component of MS risk, but each gene in isolation carries only a small risk.

Because of this, it’s not possible to generate a “genetic risk score” that accurately conveys the risk any given person has of developing MS. So we cannot single out the individuals who are at greater risk, even if we know how many of them might exist in the community.

When myelin is damaged, messages can no longer be clearly transmitted from the brain and spinal cord to other parts of the body.
from shutterstock.com

Researchers are now trying to adopt a more sophisticated genetic approach to help identify individuals at risk by focusing on families who have more than one relative with the disease. We know, in some instances, family members who don’t have symptoms could still harbour asymptomatic disease. This could mean the MS is either at an earlier stage, less severe or “blocked” before it has become clinically overt.

Identifying mutations common to affected family members could help understand the genes likely to be directly relevant to the cause of MS. The unanswered question is whether findings in families can be extrapolated to the general population.

Viruses

There is a strong association between the Epstein-Barr virus, which often results in glandular fever in young adults, and development of MS. If you have not been exposed to the virus, you will likely not get the disease.

There are many theories for how the virus may be implicated in MS. The virus infects a type of white blood cell important for the immune system. Infection of the cell could then cause corruption of the immune response, which could lead to the autoimmunity of MS.

But the Epstein-Barr virus is not sufficient on its own to trigger MS, as more than 90% of people who aren’t affected by MS have been exposed to the virus.

Sunlight

Sunlight, or more specifically exposure to ultraviolet (UV) radiation, decreases with increasing distance from the equator.

The further away from the equator you live the greater your risk of developing MS. In Australia, those living in northern Queensland are seven times less likely to develop MS than those in Tasmania.

Ultraviolet light is known to have many effects on the immune system and our synthesis of vitamin D. In particular, UV appears to have an impact on immune activity, making immune cells more tolerant and in some instances suppressing immune activity.

Smoking significantly increases a person’s chances of developing MS.
Mathew MacQuarrie/Unsplash

Hormones

The fact women are more likely to develop MS than men may be related to hormonal changes.

We know disease activity drops during pregnancy. We also know women who have multiple children are on average less likely to get the disease and, if they do, it is likely to be less severe.

Lifestyle

Smoking significantly increases a person’s chances of developing MS. Smokers, and people exposed to second-hand smoke, are almost twice as likely to develop MS. In particular, they are more likely to develop progressive forms of MS.

For people who already have MS, there is good evidence that stopping smoking reduces the severity of disease progression.

Although the subject of ongoing research, it would appear smoking influences the production of certain proteins in the lungs that may trigger immune cells to become more alert. At the extreme, this could set off the immune response.

What we suspect

There is a great deal of interest in the role nutrition and diet could play in the development and management of MS. These studies are complex due to the many potential nutritional components found in our diets.

It is possible that keeping cholesterol and fats in a healthy range could help MS symptoms, such as reducing levels of fatigue. However, this is an ongoing area of research.

There is stronger evidence when it comes to body weight and obesity and the risk of MS. Studies have shown that being overweight or obese, particularly during adolescence, is associated with an increased risk of developing MS. It is also associated with worse outcomes in people who have MS. Not much is known about the mechanisms that may be responsible for this.

The results of physical therapy for people with MS are varied but have been associated, at least in the short term, with some benefit, such as improved balance and coordination.

Trevor Kilpatrick, Professor of neurologist and clinical director, Florey Institute of Neuroscience and Mental Health

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Liver transplant from HIV+ living donor to negative recipient: key ethical issues

Fundamental questions of ethics are involved in donor transplant decisions.
Shutterstock

Harriet Etheredge, University of the Witwatersrand; Jean Botha, University of the Witwatersrand, and June Fabian, University of the Witwatersrand

South Africa has a dire shortage of organ donors. This means that doctors struggle to find suitable donor organs for critically ill patients who would die without receiving a transplant. Sometimes they have to make tough calls such as using a blood group incompatible organ to save a patient’s life – even if this comes with additional risk.

About a year ago we made a tough call of our own: we could save a child’s life by giving the child a liver transplant – but risked infecting the child with HIV in the process. The donor was the child’s mother, who is HIV positive and the child was HIV negative. The procedure came with a risk of transmitting HIV to the child.

South Africa’s law does not forbid the transplantation of an organ from a living HIV positive donor to an HIV negative recipient, provided that a robust informed consent process is in place. But this isn’t universally accepted as best clinical practice because of the risk of HIV transmission to the recipient.

The young recipient had been on the organ donor waiting list for 181 days. The average time on the waiting list in our transplant programme is 49 days. The child’s mother had repeatedly asked if she could donate a part of her liver, but we could not consider this because it was against the policy in our unit at the time. Without a transplant, the child would certainly have died.

After much consideration, and with permission from the Medical Ethics Committee at Johannesburg’s University of the Witwatersrand, we decided to go ahead with the transplant. With careful planning we were able to give the child antiretroviral drugs in advance, with the hope of preventing HIV infection.

The transplant, which happened at the University of the Witwatersrand’s Donald Gordon Medical Centre, was a success. The child is thriving, but at this point we are unable to determine the child’s HIV status. In the first month after the transplant we detected HIV antibodies in the child and it looked like HIV infection might have taken place. But as time went by the antibodies declined and are now almost undetectable. We have not been able to work out for certain whether the child has HIV or not. Even with ultra-sensitive, specialised testing, we have not been able to detect any HIV in the child’s blood or cells.

It will probably still be some time before we can be sure. However, the child is doing very well on antiretroviral treatment. And we know from cases where HIV was transmitted inadvertently that people who get HIV from an organ transplant do as well as those who get an HIV-negative organ.

This operation could be a game changer for South Africa. The country has a large pool of virally suppressed HIV-positive people who have previously not been considered for living liver donation. Viral suppression is when a person with HIV takes their antiretroviral medication as prescribed and their viral load – the amount of virus in their blood – is so low that it is undetectable.

Ethical and legal considerations

Organ transplant comes with many ethical and legal challenges. In this case, some unique and complex issues were carefully considered.

We took great care to consult widely before doing the transplant. This included speaking to the members of the transplant team, bioethicists, lawyers, experts in the field of HIV medicine and Wits University’s Medical Ethics Committee. The committee’s function is – among other things – to protect patients in medical research, and to make sure doctors are doing procedures for the correct reasons.

It was clear that a transplant was in the child’s best interests. The bigger ethical question was whether it was right to deny the mother the opportunity to save her child’s life. A fundamental principle of ethics is to treat people fairly. People with HIV should have the same health care options as everyone else.

We, along with the Ethics Committee, agreed that as long as the child’s parents understood that there was a risk the child could acquire HIV, it was acceptable to go ahead with the transplant.

Then, to ensure that the child’s parents were properly informed and in the best position to make a decision, we used an independent donor advocate. The advocate was not employed by the hospital and their main role was to support the parents by ensuring that they understood exactly what the risks were for the mother as a donor. The advocate also engaged with the transplant team on the parents’ behalf, if needed.

In this case, the parents were committed to go ahead with the operation, and had already come to terms with the risk of HIV transmission to their child. They were appreciative that the team were willing to carefully consider this option for them, given that there were no alternatives available and their child was critically ill. We asked both parents to consent to the procedure, as both are responsible for taking care of the child going forward.

Lessons and opportunities

This operation has shown that doctors can do this type of transplant, and that outcomes for the HIV positive donor and the recipient can be good. It has also created a unique opportunity for scientists at Wits to study HIV transmission under very controlled circumstances.

For now, doctors will not be able to tell parents whether or not their child will get HIV from this type of transplant. This is because this is a single case with many unanswered questions that will hopefully be answered through ongoing research.

Going forward, we will continue to ensure that parents are fully aware of the uncertainty in this situation. All future cases will be part of an ongoing research study that will investigate HIV transmission in children in more detail and the ways in which HIV may or may not be spread through organ transplantation.

Harriet Etheredge, Bioethicist and Health Communication Specialist, University of the Witwatersrand; Jean Botha, Head of Transplants at Donald Gordon Medical Centre, University of the Witwatersrand, and June Fabian, Research Director at Donald Gordon Medical Centre , University of the Witwatersrand

This article is republished from The Conversation under a Creative Commons license. Read the original article.

I’ve always wondered: why many people in Asian countries wear masks, and whether they work

Face masks are a common sight in Asia. Why?
David Chang/AAP

C Raina MacIntyre, UNSW dan Abrar Ahmad Chughtai, UNSW

This is an article from I’ve Always Wondered, a series where readers send in questions they’d like an expert to answer. Send your question to alwayswondered@theconversation.edu.au

In Japan, many people wear face masks – is that to prevent the wearer getting the infection, or is the wearer already infected and protecting those around? Is the mask useful in protecting against viruses or bacteria? – Petrina, Greenwich

Thanks for your question, Petrina. You’re right, in countries like Japan and China, facemask use in the community is widespread – much more so than in Western cultures. People wear them to protect the respiratory tract from pollution and infection, and to prevent the spread of any pathogens they might be carrying.

Whether this works depends on the type of mask.

There are three supposed ways a mask can provide protection: by providing a physical barrier (which prevents splashes and sprays), by filtering the particles (blocking particles of a certain size from entering the respiratory tract), and by fitting around the face to prevent leakage of air around the sides.

Some mask makers have also gone the extra step of using antimicrobials and claim to kill bugs on the surface of the mask, but these haven’t been tested to see if they provide any benefit.

Healthcare workers have been using cloth masks (made of cotton or other materials and with ties to secure them at the back) while caring for patients since the late 19th century to protect from various respiratory infections such as diphtheria, scarlet fever, measles, pandemic influenza, pneumonic plague and tuberculosis.

Cloth masks have been around since the late 19th century.
Author provided

During the mid 20th century, disposable surgical facemasks (similar in look to the cloth masks but made of paper) were developed. Surgical masks were developed to prevent the surgeon from contaminating the wound during surgery, but studies have not proven they help.

Surgical masks have no evidence of effectiveness.
from www.shutterstock.com

These were followed by respirators, which vary in shape and material but are designed to fit around the face and filter particles. Respirators are designed specifically to protect the respiratory tract from inhaled germs. There are many types, which may be reusable or disposable.

People must undergo fit-testing to ensure respirators are correctly fitted, with a good seal around the face. Unlike masks, respirators are subject to certification and regulation, and are proven to protect against respiratory infection.

Respirators are proven to protect against infection.
from www.shutterstock.com

Surgical masks are unregulated for filtration and do not fit around the face, and the evidence for their use is less convincing. In a community study, families with a sick child who wore such a mask were less likely to get sick if they also wore a mask, but many family members didn’t wear their masks all the time.

In a university setting, students were protected from sick classmates if they wore the mask within 36 hours of their classmate getting sick.

In many low income countries, the cost of even paper surgical masks is prohibitive, so cloth masks are used, washed and re-used. But these don’t protect against infection, and may even increase the risk of infection.

Prevention of infection vs source control

Masks can be used to protect healthy people (such as nurses and doctors) from exposure to infection, but are also used by sick people (such as a TB patient) to prevent spread of infections to others (called “source control”). There is less research on this use than on the use of masks by well people. The efficacy of source control is unknown.

Do masks work?

It’s long been thought surgical masks protect from transmission of pathogens, which spread through the air on large, short-range droplets, while respirators protect against much smaller, airborne particles, which may remain suspended in the air for several hours and transmit infection over long distances. So most guidelines recommend a mask for droplet transmitting infections (such as influenza) and a respirator for airborne infections (such as TB and measles).

But we’ve shown respirators protect better than masks even against droplet-spread infections. And the longstanding belief that infections neatly fit into either droplet or airborne transmission is not correct. Respiratory transmission of infections is more complex than this.

To say whether masks work, we have to specify whether we’re talking about a respirator, a surgical mask or a cloth mask.

The respirators are the Rolls Royce option and do protect, and this is a tool for frontline health workers facing epidemics of known and unknown infections. Surgical masks probably also protect but to a lesser extent. But there’s no evidence cloth masks will protect against invading or escaping bugs.

* Email your question to alwayswondered@theconversation.edu.au

* Tell us on Twitter by tagging @ConversationEDU with the hashtag #alwayswondered, or

* Tell us on Facebook

C Raina MacIntyre, Professor of Infectious Diseases Epidemiology, Head of the School of Public Health and Community Medicine, UNSW dan Abrar Ahmad Chughtai, Epidemiologist, UNSW

Sumber asli artikel ini dari The Conversation. Baca artikel sumber.

Cracking the sugar code: Why the ‘glycome’ is the next big thing in health and medicine

By molekuul_be/shutterstock.com

Emanual Maverakis, University of California, Davis; Carlito Lebrilla, University of California, Davis, and Jenny Wang, Yeshiva University

When you think of sugar, you probably think of the sweet, white, crystalline table sugar that you use to make cookies or sweeten your coffee. But did you know that within our body, simple sugar molecules can be connected together to create powerful structures that have recently been found to be linked to health problems, including cancer, aging and autoimmune diseases.

These long sugar chains that cover each of our cells are called glycans, and according to the National Academy of Sciences, creating a map of their location and structure will usher us into a new era of modern medicine. This is because the human glycome – the entire collection of sugars within our body – houses yet-to-be-discovered glycans with the potential to aid physicians in diagnosing and treating their patients.

Thanks to the worldwide attention garnered by the 2003 completion of the Human Genome Project, most people have heard about DNA, genomics and even proteomics – the study of proteins. But the study of glycans, also known as glycomics, is about 20 years behind that of other fields. One reason for this lag is that scientists have not developed the tools to rapidly identify glycan structures and their attachment sites on people’s cells. The “sugar coat” has been somewhat of a mystery.

Until now, that is.

While most laboratories focus on cellular or molecular research, our lab is dedicated to developing technology to rapidly characterize glycan structures and their attachment sites. Our ultimate goal is to catalog the hundreds of thousands of sugars and their locations on various cell types, and then to use this information to tailor medical therapies to each individual.

Why do we care about glycans?

In the future, it is likely that analysis of an individual’s glycans will be used to predict our risk for developing diseases like rheumatoid arthritis, cancer or even food allergies. This is because glycome alterations can be specifically tied to particular disease states. Also, biological processes like aging are linked to inflammation in our glycome. It remains to be tested if reversing these changes can help prevent disease, or even slow aging – an intriguing possibility.

Along with DNA, proteins, and fats, glycans are one of the four major macromolecules essential for life. Of these four, glycans are the final arbiters of how our cells behave.

DNA orchestrates what we look like, our capacity to think and behave, and even determines the diseases to which we are most susceptible. Within our DNA are short segments, genes, which often contain instructions for how to synthesize proteins. Proteins in turn are the “workhorses” of the cell, carrying out many of the functions necessary for life.

However, how a protein behaves often depends on what glycans are attached to it. In other words, these sugar molecules can greatly influence how our proteins do their work, and even how our cells will respond to stimuli. For example, if you change a few glycans on the outside of a cell, it might trigger that cell to migrate to a different location in our body.

The main job of glycans is to modify the proteins and fats that sit on the surface of our cells. Together, they create a thick sugar coat around the cell. If we consider the surface of the cell to be soil, then glycans would be the wonderfully diverse plant-life and foliage that sprout up and bring color and identity to the cell. In fact, if you were able to see a cell with your naked eye, it would look very fuzzy. Picture a peach with 10 times more fuzz.

Every single cell in the human body is covered with a collection of glycans which are assembled using various simple sugars like glucose, mannose, galactose, sialic acid, glucosamine and frucose as building blocks. By sensing the type of sugar coat present, our immune cells can identify other cells as friend or foe. This is because bacteria have sugars on their surfaces that are never seen on human cells – the pathogen’s sugars are sensed by the immune system and that identifies the bacteria as ‘foreign.’
Emanual Maverakis, CC BY-SA

Glycans label our own cells and identify them as ‘self’

The fuzz around a cell is its glycan coat. Being on the outside of our cells, glycans are the first point of contact for most cellular interactions and thus influence how our cells communicate with one another. You can also think of the glycans as a unique cellular “barcode.” Thus, a kidney cell’s fuzz will look different from an immune cell’s fuzz. But there are also similarities. In fact, the immune cells that survey our body searching for pathogens know not to attack our own “self” cells because of common features in the glycan “barcode” which are shared by all cells of our body.

In contrast, bacteria and parasites like malaria have different “sugar coats” that are not seen on human cells. When bacterial sugars are tagged as “foreign,” a person’s immune system targets the bacterium for destruction. However, some harmful bacterial pathogens like group B streptococcus, which commonly cause severe infections in babies, can avoid immune detection by impersonating human cells by carrying similar glycans as a disguise – like the wolf dressed in sheepskin.

Unfortunately some pathogens are also able to use our glycans to help them cause disease. Deadly viruses like HIV and Ebola have evolved to grab hold of specific glycans which they then “lock” onto as they infect our human cells. Therapies that either block these viruses from interacting with our glycans, or that attack virus-specific glycans may be a new avenue to treating these infections.

The sugars on our cells and on bacterial cells label them as friend or foe.
Emanual Maverakis, CC BY-SA

New research has also shown that glycans play a huge role in the development of autoimmune diseases like rheumatoid arthritis and autoimmune pancreatitis. This is not surprising since glycans directly influence the function of immune cells.

Normally, our immune cells act as our body’s “defense system,” and identify and destroy foreign invaders like harmful bacteria or viruses. But when the body mistakenly labels our own cells as the enemy and launches an internal attack on itself, autoimmunity is born. Interestingly, in such instances, it is the glycans present on the misbehaving self-attacking antibodies that will dictate the strength of the attack on the body. This abnormal immune response can even be directed against glycans. For example, the immune system can mistake “self” glycans as if they were “foreign” molecules. Our research team recently published an article that introduced the glycan theory of autoimmunity, which explains some of these relationships.

Glycans in our food can trigger immune responses

There have been many studies linking consumption of red meat with diseases like atherosclerosis and diabetes, but they have not been able to show why or how this occurs until recently. One intriguing study suggests that the culprit was a sugar with the unwieldy name, nonhuman sialic N-glycolylneuraminic acid, or Neu5Gc for short. Neu5Gc is found in all mammals except humans, because the early humans that could make Neu5Gc died from an ancient malarial parasite.

However, although we now lack the ability to produce Neu5Gc, our bodies still have the ability to incorporate it into the glycans on our cells if we obtain it by eating red meat. Once it becomes part of our cells’ glycan coat, our cells then have a “foreign” substance – Neu5Gc – surrounding them. This can trigger inflammation throughout the body because our immune system recognize Neu5Gc as “foreign” and attacks it. The chronic inflammation caused by these internal attacks can lead to heart attack, stroke and even cancer.

Our bodies synthesize tens of thousands of unique glycans, often with branching structures formed from simple sugar building blocks. Proteins or fats can also be modified by dozens of unique glycans. These countless combinations make mapping glycans a difficult task because we need a practical and efficient way to analyze hundreds of thousands of glycan patterns.

Our research team has now developed methods to rapidly and robustly monitor the human glycome. By capitalizing on engineering advancements and improvements in sample processing, our technique can monitor thousands of glycans at once, which allows us to characterize the glycans in cells from healthy controls and patients with a variety of different diseases. Our goal is to use this data to develop predictive models to help clinicians diagnose and treat all human diseases. We believe that a new wave of medical advancements will arrive as we unlock the “sugar code.”

Jenny Wang was the co-lead author of this article.

Emanual Maverakis, Associate Professor- Departments of Medical Microbiology & Immunology and Dermatology | Member- Foods For Health Institute | Member- Comprehensive Cancer Center | Director- Autoimmunity | Director- Immune Monitoring Core, University of California, Davis; Carlito Lebrilla, Distinguished Professor of Chemistry, University of California, Davis, and Jenny Wang, Clinical Research Fellow, University of California, Davis | Medical Student, Albert Einstein College of Medicine, Yeshiva University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

How an app is helping to collect genetic data in Ethiopia and Ghana

Genetic data holds a wealth of health information.
CI Photos/Shutterstock

Shane C Quinonez, University of Michigan

Genetic technologies are poised to change the world. Want to eradicate a human disease such as cystic fibrosis or improve a person’s ability to run impossible distances or lift unimaginable weights? This may be possible in the future by using something called CRISPR to edit an organism’s genetic makeup. How about rapidly sequencing a newborn’s genome, similar to an early scene in the 1997 movie Gattaca? Next-generation sequencing may make this fiction a reality.

As these technologies continue to increase in ability and decrease in cost, we may soon be living in an age of genomics-informed health care.

Unfortunately, the “we” in the previous sentence only applies to at best 7% of the world’s population. For everyone else technologies such as next-generation sequencing and CRISPR gene editing are more science fiction than nonfiction.

Low or middle-income countries are where this technology is needed the most as they harbor the largest burden of birth defects and genetic diseases. Yet almost all low-income countries and many middle-income countries lack the necessary personnel, technology, infrastructure, and public and medical education capabilities needed to introduce medical genetics services.

To address this gap, my colleagues and I created the MiGene Family History App. It’s an Android-based mobile application that aims to introduce medical genetics services into low and middle-income countries.

The app is used by health care providers and collects and stores patient and family histories. It generates personalised genetic counselling information that can be delivered to patients and their families. And the data can also be used for epidemiologic analysis.

The app has already been piloted in an Ethiopian hospital and has since been rolled out to a teaching hospital in Ghana.

It’s important to point out that the technology the app uses is far from what’s required to perform genome sequencing or gene editing in Ethiopia. But our work is one of the many preliminary steps needed to bring attention to the need for genetic services in low and middle-income countries.

Pilot project in Ethiopia

The MiGene Family History App was designed jointly by teams at the University of Michigan and St. Paul’s Hospital Millennium Medical College in Addis Ababa. It was then programmed by xHub, a technology group in Ethiopia’s capital.

The first version of the app focuses on paediatric birth defects and genetic diseases. These include heart malformations, Down Syndrome, and neural tube defects. So we launched the app in the Paediatric and Obstetrics and Gynaecology departments at St. Paul’s. We also conducted a study about the app’s value and ease of use.

MiGene was loaded onto physicians’ and nurses’ tablets. It was then used to collect data in both departments, but with a focus on the general paediatrics ward. The staff told us they found the app easy to use. The app allowed us to provide the hospital with data on the incidence of birth defects and genetic diseases in the institution. For instance, we found that approximately 12% of all admitted patients were affected with a birth defect or genetic disease. Heart malformations and Down Syndrome were the most common conditions present.

Having this data will help to inform future decisions taken by Ethiopia’s ministry of health. For instance, it can assess the success of interventions such as the country’s folic acid supplementation efforts, which were introduced as a strategy to decrease the incidence of birth defects of the brain, spine, or spinal cord.

While our study was intentionally small in scope, if use of the MiGene Family History App is expanded to other regions within Ethiopia it will provide more representative population data.

One of our most interesting findings was that the incidence of birth defects and genetic diseases at St. Paul’s was nearly identical to the incidence of birth defects and genetic diseases in previously studied children’s hospitals in high-income countries.

This confirms something that geneticists have long known: genetic disease affects everyone and doesn’t discriminate. That’s why it’s so crucial that the benefits of genetic technology are not limited to only those individuals fortunate enough to have been born into a rich country.

Taking the tech further

After the success of the pilot study in Ethiopia, MiGene Family History App has been expanded to include adult-onset non-communicable diseases such as cancer, hypertension, diabetes, and cardiovascular disease. It’s still in use at St. Paul’s and is now also being used at Korle Bu Teaching Hospital in Accra, Ghana.

Our future plans include improving the genetic testing capabilities available at St. Paul’s and launching a genetic counselling training curriculum at the hospital. This focus on patient and health care provider education is vital when introducing a new medical technology, such as genetic testing, into a country or region.

Shane C Quinonez, Biochemical Geneticist, University of Michigan

This article is republished from The Conversation under a Creative Commons license. Read the original article.