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Dr. Michael DiGiorno, Director of St. John’s Medical Group: Now is the Time to Catch up with Preventative Health Care, Testing – Yonkers Times

July 6th, 2021 1:55 am

Dr. Michael DiGiorno

By Dan Murphy

With most Westchester residents vaccinated, and with COVID-19 positivity rates at less than 1%, Dr. Michael DiGiorno, Medical Director of St. Johns Medical Group, is encouraging patients and our readers to return to their pre-COVID routine of getting tested, including getting their annual physicals, screening colonoscopies, bone density testing and mammograms.

Its important not to let your health lapse because of the pandemic any longer. At least come in and have an annual physical and ensure that your health screening tests are up to date. It is an extraordinarily safe time for patients to come in and catch up with their health care needs, and we are here to help them through the testing process.

Part of our challenge during the COVID-19 pandemic was to make sure that we stayed open, and that we continued to deliver care to Yonkers and the surrounding communities. We thought it was crucial to maintain a presence in the community during a very difficult time, and if you had an underlying medical condition, or had a medical question or needed a prescription refill, we were open for in person and telemedicine appointments. We concentrated on the safety of our physicians and staff and made sure we were all protected, and we did so quite successfully, said Dr. DiGiorno.

Now we are moving towards a return to normalcy. People are vaccinated and we can accommodate more patients in person. We are maintaining processes in place, including using masks and enhanced cleaning to ensure optimal safety. We provide a very safe, clean environment, so now is the time to pivot and focus on health care maintenance.

Our physicians and staff are available and understand that not everyone has the same level of comfort. If you have any specific concerns, let us know and we will work to ensure your return is a positive experience. In addition to primary care, our specialty physicians are on-site and available to address your gastroenterology, nephrology, physical medicine, vascular, podiatric and pain management needs.

Dr. DiGiorno stressed that, unfortunately, underlying health conditions dont wait for the pandemic to pass. We do see some patients, with diabetes who have strayed and have weight gain because of a lack of activity. As a result, their diabetes has become poorly controlled. Similarly, we are seeing patients with chronic hypertension, which was once well-controlled, now require additional therapy. We understand whygyms were closed, our diets and routines were interrupted, and we were told to stay home, and it all took a toll on our health.

Now is the time to get people back on track, with basic testing, and diabetes and blood pressure treatments and screenings. While we have seen some slippage with chronic conditions in some patients, we want that to be the exception and not the rule.

So go back for your basic labs, physicals, and colonoscopies. The environment is safe and clean and accessible. They will expedite your appointment and connect you to your primary care physician. If you do not have a physician, St. Johns has lots of options and it all starts with a phone call.

We understand what our community, and the world has been through. There is no judgement here. Our goal is to achieve wellness, so dont be afraid to see a physician. We just want everyone to get well again, and move forward as a community said Dr. DiGiorno.

Michael DiGiorno, DO, MHSA, FASN, is the Vice-President, Medical Operations, and the Chief of Nephrology at St. Johns Riverside Hospital, and the Medical Director of the St. Johns Medical Group practice.

To make an appointment or contact a member of St. Johns Riverside Hospital, or St. Johns Medical Group call 914.964.4DOC.

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The major health care and cybersecurity risk of ‘Right-to-Repair’ laws | TheHill – The Hill

July 6th, 2021 1:55 am

Just like other devices we rely on, medical devices can improve our quality of life so long as they are maintained to work properly. When they are not or not maintained or serviced in line with FDA approval there can be huge health care and cybersecurity risks.

In the brief on a just-released FDA discussion paper, William Maisel, notes,Many medical devices are reusable and need preventative maintenance and repair during their useful life; therefore, proper servicing is critical to their continued safe and effective use.Maisel, M.D., is the director of the Office of Product Evaluation and Quality in FDAs Center for Devices and Radiological Health.Who could possibly disagree with such a statement? Lawyers.

Thats right, the tort bar is prioritizing profit over patient safety. For shame. (No, Im not surprised either.)

Quality is the glue that holds together our health care technology ecosystem. Whether its a medicine for high blood pressure, a COVID-19 vaccine or a medical device such as an implantable stent or a room-size MRI machine, the FDAs mission rests upon a triad of trust safety, effectiveness and quality. And the bedrock upon which quality rests isGood Manufacturing Practices. Who could be against that? Lawyers.

Considerthe recent spate of suggested state and federal legislationon what is called Right-to-Repair. At first glance, it seems like a good idea. Why not make it easier for consumers to fix their broken electronics, without having to pay a costly sum to the original manufacturer? But, as HL Mencken reminds us, for every complex problem there is an answer that is clear, simple, and wrong. The reality is that Right-to-Repair presents many dangerous unintended consequences. The No.1 problem is that it compromises patient safety.

The core of Right-to-Repair laws is to require innovative technology companies to make product repair information, replacement parts and tools readily available to consumers and third-party repair shops. Should that be the case for devices such as Automated External Defibrillators and hospital ventilators? What about electrocardiograph (ECG) machines? Can physicians and patients be confident in non-FDA compliant vendors without the advanced training and technical ability to properly repair and recalibrate life-saving machines? Who could argue that anyone can do it? Lawyers.

Why? Because when things go wrong, when medical devices fail, when patients and their families suffer the consequences, when associated health care costs skyrocket it seems lawyers see opportunity. And they aim their lightening lances of litigation at the deepest pockets the original manufacturers.

It seems the tort bar is creating a problem they can exploit for profit.

But wait, it gets worse. By allowing third parties without any FDA competence to repair regulated, complicated medical devices, Right-to-Repair also opens the door to breaches in cybersecurity.

According to the FDA, cybersecurity is a widespread issue affecting medical devices connected to the Internet, networks, and other devices. Cybersecurity is the process of preventing unauthorized access, modification, misuse or denial of use, or the unauthorized use of information that is stored, accessed, or transferred from a medical device to an external recipient.

In the just-released FDA discussion paper that I referenced above, Strengthening Cybersecurity Practices Associated with Servicing Medical Devices: Challenges and Opportunities, the agency asks, How can entities that service medical devices contribute to strengthening the cybersecurity of medical devices?

According to the discussion paper, FDA defines service to be the repair and/or preventive or routine maintenance of one or more parts in a finished device, after distribution, for purposes of returning it to the safety and performance specifications established by the original equipment manufacturer (OEM) and to meet its original intended use.

In other words, the first step in advancing medical device cybersecurity is to limit and ensure that those who control repairs and maintenance of these highly sophisticated pieces of health care technology are regulated FDA manufacturers.

On July 27, the FDA is holding a public meeting on this topic. It couldnt be timelier. The proper servicing and security of medical devices and other health care technologies mustnt be subsumed for profit.

Peter J.Pitts, a former FDA Associate Commissioner, is president of the Center for Medicine in the Public Interest and a visiting professor at the University of Paris School of Medicine.

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Discovery could inform new preventive treatment for blood clots – Health Europa

July 6th, 2021 1:55 am

Researchers from the University of Leeds and the University of Sheffield have discovered a key mechanism in preventing the escalation of blockages caused by blood clots.

A blood clot forms a pulmonary embolism or blockage, cutting off blood flow to major blood vessels in the lungs. In many cases, the blockage is caused by fragments that have broken away from a blood clot elsewhere in the body, such as a deep vein thrombosis in one of the legs. The fragments are transported to the lungs via the blood stream. Now, researchers have discovered that the protein fibrin plays a key role in stabilising the original clot to prevent bits of clot from breaking loose.

The findings from the research, which was funded by the British Heart Foundation, have been published in the scientific journal PNAS.

The research team used animal studies involving mice to investigate a key chemical building block of the clotting protein fibrin, known as -chain cross links. The scientists found that the -chain cross links give the fibrin its stability through enhanced resistance to rupture and clot fragmentation.

The study examined clot behaviour in mice that were genetically modified so they could not produce the stabilising -chain cross links in the fibrin, and compared them with mice that could.

The results revealed that the clots without the -chain cross links were more unstable and more likely to fragment and produced more associated embolisms.

Dr Cdric Duval, the studys lead author and lecturer in the School of Medicine at Leeds, said: What we believe is happening is that, without the -chain cross links, the fibrin is not strong enough to hold the clot in place against the forces generated in the body from muscle movement and from blood flow.

Professor Robert Arins, also from the School of Medicine at Leeds, who supervised the research, said: The findings reveal the importance of the -chain cross links. These are the structural supports in the fibrin that keep the clot in place.

By identifying the structural dynamics of this mechanism, we have identified new targets for drugs that could be developed to stop fragments of a thrombosis breaking away to cause an embolism in the lungs.

This is a disease that is a major cause of disability and death around the world.

The research findings confirm the long-held suspicion by Professor Arins that the structure of fibrin plays a role in the fragmentation of clots but, until now, there was no scientific evidence.

He said: I have always thought that the remarkable elasticity of fibrin, which has been described as like rubber or spider silk, would be important to prevent clot fragmentation and thus thromboembolic disease.

I was astounded to see the level of differences in pulmonary embolism that resulted from a genetic mutation that resulted in reduced elastic recovery of the fibres. So, when I saw the results, it definitely was a wow moment and I also had the I told you so feeling.

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RWJBarnabas Health Pioneers Innovative Pancreatic Cyst Surveillance Program – OncLive

July 6th, 2021 1:55 am

Pancreatic cancer accounts for 3% of all new cancer diagnoses, but is the fourth leading cause of cancer death in the United States.5 Therefore, it is imperative that we, as a community, focus our efforts on learning more about precancerous conditions within the pancreas and the early identification of cancers; pancreatic cysts are an ideal target. There are 2 key components to remember with regard to pancreatic cysts: accurate identification and evidence-based longitudinal surveillance. Unfortunately, an ongoing issue for this patient population is that many are never appropriately identified or followed. However, even when identified, many patients are not referred to a pancreatic center of excellence, a gastroenterologist who focuses on the pancreas, or a surgeon with experience in pancreatic cysts. As a result, these patients can re-present years later with a pancreatic cancer.

Our institution, Saint Barnabas Medical Center, an RWJBarnabas Health Facility, in conjunction with the Rutgers Cancer Institute of New Jersey, has made efforts to focus on preventative care. Specifically, we have recently focused our attention on pancreatic cysts and partnered

with Eon to develop and implement a platform called Essential Patient Management (EPM) Pancreas to identify patients with a pancreatic abnormality, and then, longitudinally follow them using an innovative and modern cloud-based platform that includes automatic patient and physician reminders.

Through the adoption of Eon EPM Pancreas, patients who now undergo either ultrasound, computed tomography, or magnetic resonance imaging in our Emergency Department, inpatient setting, or outpatient imaging facility, will be automatically identified if they are found to have an abnormality within their pancreas. The patient will then be contacted by one of our preventative medicine nurse navigators with a phone call and a letter; they will also be offered consultation with our pancreatic care team. Additionally, the patients ordering physician will also be contacted with a letter and a call. This algorithm links all parties together and lets them know about the pancreatic abnormality that may harbor precancerous potential. This automatic identification and population of cyst factors into the cloud-based platform accomplishes the first key component to remember with these cysts.

The second component is accomplished through individual risk stratification. The pancreatic cyst size, tempo of growth, pancreatic duct caliber, mural nodularity, evidence of pancreatitis, tumor markers, pancreatic cyst fluid aspirate for carcinoembryonic and amylase levels, and, at times, genetic mutations are added to the Eon EPM dashboard. Putting these factors together, along with national and international guidelines, we determine how to best manage and follow a particular patient. Previously, this has been done by using an Excel spreadsheet. However, now, with the EPM platform, we can advance healthcare and manage patients electronically; the cloud-based system embeds into our institutions electronic medical record (EMR) system, and with that, all the aforementioned factors can be seen immediately at the time of consultation. Moreover, we have extrapolated the method of a tumor board into our pancreatic cyst clinic and we now have a weekly pancreatic multidisciplinary conference where we discuss our patients with pancreatic cysts, thus providing them with a multidisciplinary/team approach.

Eon EPM offers the most powerful Pancreas solution that uses best-in-class technology to identify incidental pancreatic abnormalities, and longitudinally track patients who require serial surveillance. Eon EPM uses sophisticated proprietary models, referred to as Computational Linguistics data science models, to positively identify incidentally found pancreatic abnormalities with 93.9% accuracy; this high accuracy rate means fewer missed patients and less coordinator effort. Moreover, EPM can integrate with any facilitys EMR and IT system, and through Robotic Process Automation, it automates many mundane and repetitive tasks.

Eon EPM Pancreas detects incidental pancreatic abnormalities noted in radiology reports, extracts pertinent information from these reports such as pancreatic cyst characteristics, enters all information into one dashboard for serial surveillance, ensures patients are tracked and followed according to evidence-based guidelines, segments and prioritizes patients based on risk stratification, and triggers follow-up.

In summary, there are 2 overarching goals of this program. The first is to improve the quality in identifying patients with pancreatic cysts and longitudinally following them to ensure that they do not fall through the cracks within the community in which they are being served. The second goal is to offer patients surgery only when it is indicated because the great majority of pancreatic cysts only require lifetime surveillancenot an operation. If we can identify high-risk pancreatic cysts and surgically remove them prior to the development of pancreas cancer and prevent other patients from having an unnecessary operation, we believe that to be a massive improvement in how patients are being cared for. I have no doubt that Eon EPM Pancreas Solution will change the landscape for patients with pancreatic cysts and tumors, and have a true impact on survival from pancreatic-related diseases.

Russell Langan, M.D., is chief of Surgical Oncology and Hepatopancreatobiliary Surgery at Saint Barnabas Medical Center (SBMC), an RWJBarnabas Health facility, and surgical oncologist at Rutgers Cancer Institute of New Jersey.

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Pet Owners encouraged to take Precautions during 4th of July Weekend – exploreokoboji.com

July 6th, 2021 1:55 am

(Okoboji)-Pet Owners are urged to take precautions during the holiday weekend, KUOO's Becky Thoreson has details:

Pet Owners encouraged to take Precautions during 4th of July Weekend

Pet Experts are urging owners to take extra care with pets during the 4th of July holiday weekend.

Kristi Henning, Director of the Emmet County Animal Shelter says it's best to take preventative measures. "You can prevent some fear anxiety in pets from something as turning up the radio or the TV really, really loud to try to drown out the sound of the fireworks. You can do a thunder shirt, if you have one. A lot of times that snug feeling of that thunder shirt gives them comfort. If you don't have one , you can pop on Pinterest, and they'll actually show you how to make one out of an old tee shirt or a wide ace bandage. It's pretty simple, it's basically just making something snug on them so they feel safe. Another alternative is to contact your vet, and ask them what sort of medicine you could give them as a preventative to an anxiety reaction."

She notes that it's important to secure your pet, and have identification. "Definitely make sure they're secured, that's important. Also, some kind of ID. If you don't have a tag on your pet and you don't have time to get one, even just taking a piece of duct tape and write your name and phone number on it, and then wrap that around their collar so taht they have something on them. Long term though, getting appropriate tags helps all the times of the year and microchips can never get lost."

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Landlords in peril, tenants in distress: Expiring eviction bans foreshadow national reckoning – The Real Deal

July 6th, 2021 1:55 am

Seven states will lift their eviction bans next month, and the cases to follow will offer a glimpse of the onslaught to come. (iStock)

In Connecticut, real estate attorney Ori Spiegel hadnt heard much from landlords as the end of his states eviction ban approached. He expects that to change, starting today.

There are many who Ive asked to call me back on June 30, Spiegel said. The governor has often waited until the last minute to extend the moratorium, so I dont really have information for them until that point.

Barring any 11th-hour interventions, Connecticut, Kentucky, North Carolina and Oregon are set to drop their state eviction protections at midnight. Four more states plus the District of Columbia are slated to do the same in July.

The expiring bans will leave the overwhelming majority of U.S. tenants whove fallen behind on rent with only the federal moratorium imposed by the Centers for Disease Control, which offers less protection and gives landlords more ways to circumnavigate.

In states without protections, eviction cases filed this month will offer a glimpse of whats to come when the federal moratorium sunsets July 31. Tenant advocates and landlord attorneys expect an onslaught of cases for arrears each in the tens of thousands of dollars that could carry astronomical costs for communities left with the job of housing the newly homeless.

Landlords in the 15 states that maintained their own bans before June 30 have largely had their hands tied when it comes to filing eviction cases. In Connecticut, the state moratorium affords a few exceptions, such as for tenants who owe back rent from before the pandemic. But Spiegel has advised landlords not to take anything to court until the state ban lifts.

Thats because the CDC moratorium offers a workaround for landlords.

The federal ban only protects tenants if they fill out a hardship declaration. In Connecticut, a judge may determine a tenants form isnt credible, paving the way for eviction.

The CDCs moratorium also includes five exemptions, the last of which has allowed eviction cases to proceed. If a tenant violated a lease for a reason other than non-payment, the landlord can bring them to court. Attorneys in states with expiring bans expect more of these cases in the next month.

States with weaker protections like North Carolina, or those without a state ban, like Florida, have already seen tenants evicted for reasons other than non-payment.

James Surane, a North Carolina attorney, said hes taken on a steady stream of cases in which the tenant had owed money, and had an expired lease, allowing the landlord to move forward with a case. And Florida attorney David Winker said the recent mass eviction of 200 tenants from a Miami building owned by apartment giant Aimco and spinoff Air was also a non-monetary action.

And for cases that are brought over arrears, the CDCs ban doesnt stop a filing in its tracks or a court from issuing a judgment. It just prevents tenants from being kicked out of their homes.

Portland, Oregon, tenant attorney Troy Pickard expects that in situations where a judge has ruled against a tenant in an eviction case, the parties wont need to go to court once the federal ban expires. The judge will be able to issue a notice that makes the eviction effective.

The sheriff will be able to go to that home and rip the people out of the house, Pickard said.

In most states, even those like New York and California that have extended eviction proceedings through the summer and beyond, the end of the federal ban will also bring an influx of filings.

About 11 million renters about 1 in every 33 Americans are estimated to be behind on their payments, according to estimates by the Center on Budget and Policy Priorities. In cases that have already been brought, the arrears owed are record-breaking.

Ive been doing this for about 30 years; probably did a half a million evictions and Ive never seen ledgers like these, Surane said. They are now topping $20,000 in arrears

Theres no comprehensive data on U.S. eviction filings. The Eviction Lab at Princeton University, which tracks five states and 29 cities, has found nearly 385,000 evictions filed since the start of the pandemic. Still, anecdotes from attorneys point to a much bigger backlog of cases.

For the landlords doing the filing, an eviction is often an act of desperation a last resort to regain financial control after as many as 15 months of non-payment.

Of the 10 million to 11 million small landlords HUD estimates are in the U.S., one-third are at risk of bankruptcy or foreclosure because of unpaid rents, the Washington Post reported.

In California, where the governor just extended rental protections until Sept. 30 one of the longest state bans nationally landlord advocates fear that smaller landlords owning four to eight units could be facing foreclosure.

Its hard enough for landlords to miss a couple of months of rent payments, but to have this go on for over a year, it has put property owners in financial peril, said Daniel Yukelson, executive director of the Apartment Association of Greater Los Angeles, which represents landlords.

Bidens decision last week to extend the federal moratorium until July 31 probably wont raise the risks for landlords by much. But the extension will add to the growing ire of property owners, particularly landlords who kept up with mortgage and bill payments by going into debt or tapping into retirement accounts because their tenants couldnt or wouldnt pay the rent.

Winker said one of his clients, a model and single mother who emigrated from Russia, was incredulous at the extended ban.

She didnt know it was coming, he said. And when she heard about it, she said this is like socialism, but its not the government that pays for it, its the landowner.

Older people just over one-third of landlords owning two- to four-unit buildings are also suffering. Many are retired and unlikely to have another source of income apart from rent, according to The Urban Institute.

A subset of owners is itching to sell. Some are scarred from the stress of the last year and want to get out entirely. Others are hoping to take advantage of the hot market, but cant unload property while their tenant is in possession. Connecticut attorney Mark Sank said he gets calls daily from owners looking to sell and tells each to wait until the state moratorium lifts.

In states where tenant occupancy isnt an issue, landlords have sold to institutional investors who will then have to take tenants who owe back rent to court.

To describe what may happen when the federal ban finally lifts, tenant advocates have relied on a grab bag of flood metaphors a wave, a deluge, a tsunami to predict the number of evictions that will ensue.

For landlord attorneys, the rental housing market itself is sick, an economic manifestation of Covid-19, and evictions are just triage. And waiting only makes it worse.

Winker compared it to preventative medicine. Take your 10-cent-per day blood pressure medication because if you dont, youll face much worse consequences.

I will end up in the hospital in the emergency room in full cardiac arrest and that is the least efficient way for me to receive my health care, Winker said. I often talk about courts being that way.

With states struggling to dole out assistance payments, many arrears cases wont be remedied until they hit housing court the last and most expensive course.

The Cost of Eviction Calculator developed by the University of Arizona estimates that the 11 million renters at risk for eviction could cost the U.S. as much as $101 billion to care for through shelter, health care and foster care.

Eventually there has to be a reckoning of some kind. The question is how does this thing ultimately end? Pickard said. Hopefully it wont end in a mass of evictions, because if it does thats just going to be one more huge cost to society that might have been avoided through some kind of intervention.

Contact Suzannah Cavanaugh

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Starpharma whacked with $93,000 TGA fine over COVID spray ads – Sydney Morning Herald

July 6th, 2021 1:55 am

Australias medicines regulator has fined Melbourne biotech Starpharma $93,000 for advertising breaches related to its COVID-fighting nasal spray, just weeks after the UK regulator raised questions about promotions of the product.

The Therapeutic Goods Administration confirmed on Friday evening it had issued the company with seven infringement notices worth $93,200 for promoting its nasal spray Viraleze via its website and YouTube channel even though the product is not yet authorised for use in Australia.

Starpharma has been clear with investors that its product is not yet available for sale in Australia. However, its online retail site with explanations of Viraleze was available to view from Australia until recently.

The regulator said the companys advertising included a restricted representation claiming that Viraleze is an antiviral nasal spray that stops SARS-CoV-2, the virus that causes COVID-19. Any claims or references to preventing or treating a serious form of a disease, condition, ailment or defect are restricted representations.

In a statement to the ASX on Monday morning, Starpharma said upon receiving the infringement notices it acted quickly to block Australians from being able to view the materials that the regulator had concerns about, including preventing them from accessing the products marketing website and its YouTube channel.

The company will work closely with the TGA to resolve the current matter and how to balance the need to provide information to its shareholders about key company milestones...with requirements of the [Therapeutic Goods] Act in relation to advertising in Australia, Starpharma said.

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Starpharma is an ASX-listed pharmaceuticals developer which currently sells a range of sexual health products including antiviral condoms.

The company pivoted its research towards coronavirus in the middle of 2020 and developed Viraleze, an antiviral nasal spray, using the same active ingredient that is in its other products.

Viraleze, which has undergone laboratory testing, is designed as a preventative measure against the virus to be used as an additional layer of protection on top of mask wearing, social distancing and vaccines.

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Baby seizures: Signs, what to do, causes, and treatment – Medical News Today

July 6th, 2021 1:55 am

Baby seizures happen when an abnormal extra burst of electrical activity occurs between neurons, or brain cells, in a babys brain. These can happen for many reasons.

Causes may include brain injury, infection, and underlying health conditions, such as cerebral palsy. A babys risk of fever-related seizure is highest when they are younger than 18 months.

Sometimes, it is difficult for parents or caregivers to notice seizures in babies and young children, as they can be subtle. However, common signs include loss of consciousness and jerking of the arms and legs.

Read on to learn more about the signs and symptoms of a baby seizure and treatment.

The symptoms a baby experiences depend on the type of seizure they have.

These types of seizures are most common in the newborn period. However, these signs may resemble usual, everyday movements and may be difficult to spot. Symptoms of subtle seizures can include:

Tonic means muscle stiffness. When a baby experiences a tonic seizure, they may:

Clonic means twitching or jerking, so when a baby has a clonic seizure, they may display repeated, uncontrolled jerking muscle movements.

During this seizure, a parent or caregiver may notice the baby is clenching or twitching parts of its body, including:

This refers to a type of seizure that starts with stiffening (tonic phase) followed by jerking (clonic phase). Therefore, a person may observe symptoms of a tonic seizure followed by signs of a clonic seizure.

Learn more about seizures here.

According to The National Institute of Neurological Disorders and Stroke, when a baby is having a seizure, it is crucial to keep them away from any hard objects to reduce the risk of injury. When the area is safe, roll them onto their side to prevent choking.

Do not put anything in the babys mouth or try to stop any mouth movements, such as tongue biting, as this can injure the baby.

Call 911, or take the baby to an emergency room if they are:

Learn what a seizure looks like here.

Seizures are the most common neurological emergency in the first 4 weeks of a babys life. As many as 15 babies per 1,000 experience a seizure. Some seizures only last a few minutes and occur once, leaving no lasting damage.

When a baby experiences frequent seizures, they must receive treatment to prevent brain damage. Brain damage occurs due to the frequent disruption of brain oxygen levels and excessive brain cell activity.

Learn more about seizures in babies here.

Sometimes, when babies show signs of a seizure, they are demonstrating healthy reflexes.

The Moro reflex, or startle, reflex is a healthy part of a babys development. If a baby hears a loud sound or senses a sudden movement, they may throw their head back and suddenly stiffen and extend their arms. Parents or caregivers should not worry when they notice this behavior. Babies tend to outgrow this reflex at 36 months.

The tonic neck reflex is a movement where a baby looks to the side with one arm extended and the other bent; it may look like they are imitating holding a sword or firing an arrow. This primitive reflex first develops in the womb and helps the baby coordinate their eyes and control fine movement. Babies may demonstrate this reflex up to 9 months old.

However, while this reflex presents with signs such as eye-rolling, lip-smacking, and leg pedaling movements, these are normal movements, particularly in newborns. It is worth noting that this reflex does not present with characteristic features of a seizure, such as jerking or stiffening.

There are many causes of seizures in babies. Some may occur due to an event such as a head injury, while others could be symptoms of an infection or an underlying health condition.

Some causes of baby seizures include:

Viral encephalitis causes brain inflammation and seizures. Common viruses, such as the flu, can cause a babys temperature to rise, increasing their risk of a febrile seizure. Bacterial infections, in particular, Group B strep bacteria can cause meningitis in babies, which can present with seizures.

Learn about the differences between viral and bacterial infections here.

Sometimes babies that have a fever or high body temperature may develop a febrile seizure. They typically only last a few minutes and occur most often in young children, roughly between 6 months and 5 years.

Signs of a febrile seizure include:

Learn more about febrile seizures here.

When a baby has hydrocephalus, cerebrospinal fluid (CSF) applies pressure on the brain. It is a common condition and can also occur on its own in the womb. If a doctor uses forceps or vacuum extractors to help deliver the baby, this may injure the head and cause CSF to accumulate on the brain.

Learn more about CSF here.

Seizures are a common symptom of cerebral palsy. If a baby has cerebral palsy, they will find it difficult to control muscle. Researchers are unsure of the exact cause of cerebral palsy. However, they do know it occurs in some babies that do not receive enough oxygen.

Learn more about cerebral palsy here.

Other causes of baby seizures include:

Learn more about epilepsy in children here.

To find out what is causing the seizure, a doctor may run an electroencephalogram (EEG). This is a test that measures electrical activity in the brain. They may do this in the emergency room or as a separate appointment.

To prepare for the EEG, a doctor places metal discs on the babys head that detect and record their brains electrical impulses.

A baby may need several EEGs, so a doctor can see what their brain activity is like between seizures.

Some conditions that induce seizures may produce healthy EEG readings, so imaging tests, such as an MRI and CT scan, may be necessary to see if any structural changes or obstructions are causing seizures.

Learn about head and brain MRIs here.

If necessary, doctors may control seizures in babies with anticonvulsant medication, including:

If the seizures are due to a lack of oxygen, doctors may administer hypothermic treatment. This procedure cools the babys brain and body to prevent brain damage. They may do this if a baby experiences difficulties during birth and is not able to breathe.

Some babies may need long-term treatment to prevent seizures from recurring. A doctor needs to know the exact cause of the seizures before prescribing an effective treatment plan. For example, treatment will differ if a baby has epilepsy or is recovering from meningitis.

Learn more about meningitis in babies here.

Several types of seizures affect babies, including subtle, tonic, clonic, and febrile seizures. Some seizures are not serious and do not leave any lasting brain damage. Infection and injury are common causes of brain seizures.

Sometimes, underlying health conditions, such as cerebral palsy, can cause seizures that require long-term treatment. If a baby has a seizure and struggles to breathe or their symptoms last longer than 5 minutes, call 911 or take them to an emergency room.

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Genetic counseling program helps patients take control of their health – Medical University of South Carolina

June 24th, 2021 1:54 am

Mary Katherine Melroy, 40, was relieved when a mammogram in November 2020 determined that the lump she found in her breast wasnt a cause for concern. What was concerning, however, was her risk assessment score for developing breast cancer.

She was referred to the High-Risk Breast Evaluation Clinicat MUSC Hollings Cancer Center, where she met with a genetic counselor and completed testing to search for clues that may have put her at a greater risk of developing an inherited form of breast cancer. Thats when she learned she had a pathogenic mutation in the CHEK2 gene and a 25% to 39% chance of developing breast cancer in her lifetime more than double the risk of the average U.S. woman. The mutation also increases her risk of developing colon and thyroid cancer.

Instead of panicking, Melroy was comforted by the news. It gave her the answers shed been searching for when her mom was diagnosed with breast cancer 10 years ago at the age of 58.

It was actually a relief because it made sense, said Melroy, who never understood how breast cancer could affect someone as petite, healthy and fit as her mom. It didnt give me anxiety to know I had this mutation. It put the ball in my court to do what I need to do.

Melroy got to work researching her mutation and learned that opting to have a bilateral mastectomy a surgery used to remove both breasts could reduce her risk of breast cancer to 5%. After watching her mom struggle with the side effects of chemotherapy, she decided she wanted to do everything in her power to reduce her risk of going through the same thing. She plans to get the surgery toward the end of 2021.

Knowing shes at increased risk of cancer is empowering for Melroy, as she feels like she has options for shaping her future.

As an adult, there are very few things that I feel like I can control, but this is a piece of the puzzle of my health that I can take control of. Id rather get the surgery than go in for screenings twice a year because Id feel like we were just waiting until we found something, said Melroy, who also plans to talk with her doctor about getting screened early for colon cancer.

Theres so much you can do when you have the knowledge. A lot of people are scared at the thought of getting genetic testing, but whats scary to me is looking at what happened to my mom.

At Hollings, the demand for genetic testing has risen 422% in the last year. In response, the genetic counseling program is the largest it has ever been, employing six counselors total, two of whom provide full-time onsite services for Hollings patients.

While genetic testings popularity took off in 2013 following a Supreme Court case that allowed more than one company to test for certain genetic mutations, it continues to become more common as testing guidelines expand to include more people. Its now recommended that all pancreatic, ovarian and high-risk prostate cancer patients be referred for testing, and talks of including all breast cancer patients are in the works.

According to Libby Malphrus, one of Hollings onsite counselors, the ability of Hollings program to grow with the demand is one thing that makes it unique.

Theres a shortage of genetic counselors nationally. The access people have to genetic counselors at Hollings is huge and something most large health care systems strive for, said Malphrus. We have a multitude of counselors and various ways in which we can deliver that service, including through telemedicine, and thats a huge asset.

Because the program is still growing, genetic counseling currently is only available to current cancer patients or those deemed at high risk of developing cancer based on their family history. For patients who already have cancer, genetic testing can help to inform their treatment plans, from determining which surgical techniques should be used to how aggressively the cancer should be treated.

It can also determine whether theyre at risk of developing other cancer types and whether their family members may need increased surveillance.

While the information found can potentially be lifesaving for cancer patients and their families, Charly Harris, the programs other full-time genetic counselor, reminds patients that testing also comes with risks.

When someone is diagnosed with cancer, they dont want to think about whether there are other cancer types for which they may be at risk. Their diagnosis is often already a big surprise for them, so adding additional cancer risks can be too much information in that moment, said Harris, who noted Hollings counselors meet with patients prior to testing to discuss the pros and cons.

Malphrus added, Its hard enough for individuals to battle their diagnoses and watch the emotional impact that has on their families without the thought that they could be passing that gene on to their children. Thats heavy information, which is why we dont want anyone to assume they should be tested just because they have cancer.

Melroy understands the information found through her testing affects not only her own health but the health of her sisters, brother and children. Shes already planning on having her 6-year-old daughter tested when shes old enough.

While the technology used in genetic testing continues to grow in speed and efficiency, Malphrus and Harris acknowledge theres still a lot that is unknown about how to use the results. Finding a mutation by testing more genes isnt helpful if counselors dont know what that mutation means.

Thats why its important for patients to have testing done through a genetic counselor who is trained in medical genetic testing as opposed to companies offering direct-to-consumer DNA testing. Direct-to-consumer tests only examine a small number of genes, giving an incomplete picture of potential health risks. The test at Hollings examines up to 84 genes that are known to be associated with an increased cancer risk.

While certain cancers, like breast and ovarian, are more strongly associated with hereditary factors than others, most cancers are not inherited. In fact, only 5% to 10% of breast cancers and 20% to 25% of ovarian cancers are hereditary, which is why getting regular cancer screenings is important regardless of genetic testing results.

People often think, I dont have a family history, so its not going to happen to me, said Harris. I always remind my patients that they still have the general population risk of all cancers. Just because weve lowered the risk for hereditary cancers doesnt mean they dont need to continue getting screened.

Individuals can lower their cancer risks through lifestyle choices such as maintaining a healthy weight and diet, getting regular exercise, avoiding smoking and staying on top of their preventive care. Additionally, getting the HPV vaccine can protect against six types of cancers.

While Harris and Malphrus both entered genetic counseling due to their love of the science, they agree that the most rewarding part of their job is giving patients a sense of control over something they often feel they cant change.

Genetics is complicated, and its only becoming more complex, said Malphrus. Its rewarding to be that bridge between science and medicine and to help people to make educated choices that are best for themselves and their families.

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Genetic counseling program helps patients take control of their health - Medical University of South Carolina

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One-year-old baby in UAE receives imported genetic medicine to treat rare disease – Gulf News

June 24th, 2021 1:54 am

A one-year-old Emirati baby Afra with a progressive muscular disease has been successfully treated with an advanced genetic treatment that will prevent further deterioration. Image Credit:

Abu Dhabi: A one-year-old Emirati baby with a progressive muscular disease has been successfully treated with an advanced genetic treatment that will prevent further deterioration.

Baby Afra was diagnosed with spinal muscular atrophy (SMA), an inherited disease that damages nerve cells, called motor neurons, in the spinal cord. The most common form of the rare neuromuscular disease involves an abnormal or missing survival motor neuron 1 gene (SMN1 gene).

I first noticed abnormal movements in Afra when she was only three months old and quickly consulted a paediatric physician. After multiple tests, Afra was diagnosed with SMA, and transferred to the Sheikh Khalifa Medical City (SKMC), said Afras mother said.

Genetic medicine

The SKMC medical team sprang into action and developed a comprehensive treatment plan to prevent further deterioration. This included importing a genetic medicine, which has viral vectors that target the affected neurons, inserting copies of normal SMN1 genes inside. Following this, the muscle condition improves in terms of movement and function.

Afras journey towards recovery is a significant achievement, not just for the A u Dhabi Health Services Company (Seha) network [which includes SKMC], but for the wider healthcare ecosystem in the country, as we provide hope and create impact for families with children diagnosed with SMA, said Dr Mariam Al Mazrouei, SKMC chief executive director.

Early intervention

The key to successfully overcoming SMA is early diagnosis and implementation of a vigorous treatment strategy. This keeps the neurons as intact as possible and prevents further damage, said Dr Omar Ismail, paediatric neurology consultant and head of paediatric neurology at the hospital.

In Afras case, even though she was brought in quite late with affected limbs, we quickly jumped into action with an inclusive treatment plan that prevented further deterioration of her muscles while we waited for the required genetic treatment to arrive from abroad. This particularly helped with Afras breathing muscles, and eliminated the need for an artificial respiratory device, Dr Ismail said.

Baby Afra will continue to be followed up by doctors at SKMC.

The medical team has implemented a robust treatment plan. I am tremendously grateful to them for their diligence in treating my daughter, Afras mother said.

Prevalence

According to the Centre for Arab Genomic Studies, the prevalence of SMA in GCC populations is thought to be at least 50 times higher than in the United States, with more than 50 cases per 100,000 live births, compared to only 1.2 in the United States. It is one of the diseases that the Abu Dhabi Emirates Premarital Screening and Counselling Programme screens for, before couples wed, in order to alert couples about possible risk.

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Black and non-Hispanic White Women Found to Have No Differences in Genetic Risk for Breast Cancer – Cancer Network

June 24th, 2021 1:54 am

The findings challenge past, smaller studies that found Black women face a greater genetic risk [for breast cancer] and the suggestion that race should be an independent factor when considering genetic testing, said first authorSusan Domchek, MD,executive director of the Basser Center for BRCA.2

Investigators studied 3946 Black and 25278 non-Hispanic White women, with 5.6% and 5.06%, respectively, found to have 1 of 12 genes linked to breast cancer. The study looked at the main PVs in genes, tumor estrogen receptor (ER) status, and age.

PVs in 3 different genesCHEK2, BRCA2, and PALB2were found to be the most statistically different between the two races. For CHEK2, non-Hispanic White women were more likely to have PVs than Black women (1.29% vs 0.38%; P < .001). For BRCA2, Black women were more likely to have PVs than non-Hispanic White women (1.80% vs 1.24%; P = .005); in PALB2, more PVs were noted in Black women (1.01% vs 0.40%; P < .001).

In ER-positive breast cancer, Black women were more likely to have BRCA2 (1.56% vs 1.05%; P = .04) and were less likely to have CHEK2 (0.46% vs 1.36%; P < .001) PVs compared with white women. There was a higher prevalence of PALB2 PVs in Black vs non-Hispanic women with ER-negative breast cancer (1.83% vs 0.95%; P = .04) and triple-negative breast cancer (2.79% vs 1.23%; P = .05). BRCA1, BRCA2, and PALB2 accounted for 75% of PVs in ER-negative cases, at rates of 81.3% in Black women and 77.0% in non-Hispanic White women.

The investigators found that there was no difference in rates of PVs by age of diagnosis before 50 years (8.83% of Black vs 10.04% of non-Hispanic White women; P = .25). CHEK2 was more likely to occur in non-Hispanic White women than Black women diagnosed under the age of 50 (1.82 vs 0.43; P <.001). Adjusting for age, it was found the prevalence ration was 1.08 for the comparison of non-Hispanic and Black women (1.08; 95% CI, 1.02-1.14). In PALB2, there was a higher standardized prevalence ratio for PVs in Black women (.40; 95% CI, 0.33-0.38) whereas CHEK2 had a lower prevalence (3.35; 95% CI, 3.01-3.74) by age.

After age adjustment, there was no longer a prevalence difference found for BRCA2, with a standardized ratio of 0.91 (95% CI, 0.81-1.01). Notably, 4 PVs of ATM, BRCA1, RAD51D, and TP53 showed significant association with ethnicity when age was adjusted, whereas no such correlation was seen previously.

Investigators noted that one limitation of this study was unknown family history of patients. They also had a very small group of patients with RAD51C and RAD51D to be able to draw conclusions about prevalence.

At a time when Black men and women are more likely to be diagnosed with cancer at later stages when it is less treatable, [the Black & BRCA initiative] seeks to empower people to understand their family health history and take action to prevent cancer from one generation to the next, Domchek said.

References

1. Domchek SM, Yao S, Chen F, et al. Comparison of the prevalence of pathogenic variants in cancer susceptibility genes in black women and non-hispanic white women with breast cancer in the United States. Published online May 27, 2021.JAMA Oncol. doi:10.1001/jamaoncol.2021.1492

2. Black and white women have same mutations linked to breast cancer. News Release. Penn Medicine. June 11, 2021. Accessed June 16, 2021. https://bit.ly/3qfH6qP

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What’s in your genes | The Crusader Newspaper Group – The Chicago Cusader

June 24th, 2021 1:54 am

By Dr. DeLon Canterbury

Ever wonder why you may take a medication and have side effects, but a family member takes the same medication and does fine? Although your age, sex, weight, and health conditions could be factors

The answer may be in your genes!

Regardless of race, ethnicity, or gender, nearly 99.9 percent of EVERYONEs DNA is similar. For that 0.1 percent, there can be significant gene changes that impact how well or how poorly you tolerate a specific medication.

In other words, your DNA can affect whether you have a bad reaction to a drug, if a drug helps you, or has no effect.

Pharmacogenomics (Gene Testing/Precision Medicine) looks at how your DNA affects the way you respond to drugs. Its the study of specific gene changes that influence whether a medication could be lifesaving for one but potentially fatal for another.

The use and study of drug-gene testing has been around for 20 years. In the beginning, most insurance carriers did not cover it. Now, pharmacogenomics is widely available and affordable.

So why are you just hearing about Pharmacogenomics?

Sadly enough, health care still is not accessible to everyone, even those who have the best access still may not get the best answers!

As a concerned pharmacist with a passion for health equity and medication, GeriatRx can provide gene testing, identify potentially rare genetic disorders, as well as prevent you from taking ineffective and expensive medications.

It baffles me that the antibiotics, blood pressure, anxiety, and several other drugs we use daily were best assessed for a group of people that does not truly reflect the melting pot we proudly call USA.

Most modern, medicinal and pharmacological practices seen in our American health system stem from outdated, clinical studies with an overwhelming majority of white male subjects. Yes, we bleed the same, but how we respond to the drugs we take regularly, can be completely different!

GeriatRx has an absolute responsibility in sharing how using genetic tests can stop harmful and fatal medications from entering your body! GeriatRx works with your provider on how to best prescribe new drugs.

Want to know whats in your genes?

Get a personalized genetic test from an accessible and trusted pharmacist who can provide genetic testing anywhere in the country, GeriatRx.

Let GeriatRx advocate for you.

Dr. Canterbury, president/CEO of GeriatRx, Inc., is a Board-Certified Geriatric Pharmacist who focuses on the special needs of older patients that may have concurrent illnesses taking multiple medications. He is being trained as a Medicare and Medicaid specialist through the Seniors Health Insurance Information Program (SHIIP) and is a member of Durham, North Carolinas, African American COVID Task Force.

To learn more about GeriatRx and pharmacogenomics, contact Dr. Canterbury@cell: 404-484-5092; website: http://www.geriatrx.org; email: geriatrxinc@gmail.com.

Looking to Advertise? Contact the Crusader for more information.

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Immusoft Announces Formation of Scientific Advisory Board – Business Wire

June 24th, 2021 1:54 am

SEATTLE--(BUSINESS WIRE)--Immusoft, a cell therapy company dedicated to improving the lives of patients with rare diseases, announced today the formation of its Scientific Advisory Board (SAB) composed of world-renowned experts to provide external scientific review and high-level counsel on the Companys research and development programs.

The SAB will work closely with the Immusoft leadership team to advance and expand its leadership position in B cells as biofactories for therapeutic protein delivery, a novel approach that Immusoft has pioneered. The Company is currently preparing for the near-term clinical development of its lead investigational drug candidate ISP-001, a first-in-class investigational treatment for Hurler syndrome, the most severe form of mucopolysaccharidosis type 1 (MPS I), a rare lysosomal storage disease.

We are excited and privileged to have the opportunity to work with this group of rare disease and cell therapy experts, on the development of our pipeline, said Sean Ainsworth, Chief Executive Officer, Immusoft. These thought leaders bring tremendous understanding of rare diseases, as well as extensive experience in drug development from discovery through to late-stage clinical trials. We look forward to their continued contributions at Immusoft as we enter a new stage in advancing ISP-001 into clinical trials this year."

Members of the Immusoft Scientific Advisory Board are as follows:

Robert Sikorski, M.D., Ph.D., is Head of the SAB and consulting Chief Medical Officer at Immusoft. Dr. Sikorski currently serves as the Managing Director of Woodside Way Ventures, a consulting and investment firm that helps biotechnology companies and investors advance lifesaving technologies through clinical development. Prior to that, he was Chief Medical Officer of Five Prime Therapeutics (acquired by Amgen). Earlier in his career, he played a leading role in building MedImmunes oncology portfolio through partnering and acquisition efforts. Before joining Medimmune, he led late-stage clinical development and post-marketing efforts for several commercial drugs and drug candidates at Amgen. Dr. Sikorski began his career as a Howard Hughes Research Fellow and Visiting Scientist at the National Cancer Institute and the National Human Genome Research Institute in the laboratory of Nobel Laureate Harold Varmus. Additionally, he has served as an editor for the journal Science and Journal of the American Medical Association. Dr. Sikorski obtained his MD and PhD degrees as a Medical Scientist Training Program awardee at the Johns Hopkins School of Medicine.

Paula Cannon, Ph.D., is a Distinguished Professor of Molecular Microbiology and Immunology at the Keck School of Medicine of the University of Southern California, where she leads a research team that studies viruses, stem cells and gene therapy. She obtained her PhD from the University of Liverpool in the United Kingdom, and received postdoctoral training at both Oxford and Harvard universities. Her research uses gene editing technologies such as CRISPR/Cas9, to develop treatments for infectious and genetic diseases of the blood and immune systems. In 2010, her team was the first to show that gene editing could be used to mimic a natural mutation in the CCR5 gene that prevents HIV infection, and which has now progressed to a clinical trial in HIV-positive individuals.

Michael C. Carroll, Ph.D., is a Senior Investigator at Boston Children's Hospital and Professor of Pediatrics, Harvard Medical School. His recent research focuses on two major areas, i.e. neuroimmunology and peripheral autoimmunity. Using murine models of neuro-psychiatric lupus, his group is testing their hypothesis that interferon alpha from peripheral inflammation enters the brain and mediates synapse loss and symptoms of cognitive decline observed in patients. Following-up on a large genetic screen in schizophrenia patients, they recently reported that over-activation of a process known as complement-dependent, microglia-mediated synaptic pruning in novel strains of mice can induce psychiatric symptoms of schizophrenia. In a murine lupus model, his lab has identified that self-reactive B cells evolve with kinetics similar to that of foreign antigen responding B cells providing a novel explanation for epitope spreading. Dr. Carroll received his PhD from UT Southwestern Medical School and his postdoctoral training with the Nobel Laureate, Professor Rodney R. Porter at Oxford University. He is a recipient of awards from the Pew Foundation, American Arthritis Foundation and the National Alliance for Mental Health.

Hans-Peter Kiem, M.D., Ph.D. is the Stephanus Family Endowed Chair for Cell and Gene Therapy at Fred Hutchinson Cancer Research Center. He is a world-renowned pioneer in stem-cell and gene therapy and in the development of new gene-editing technologies. His focus has been the development of improved treatment and curative approaches for patients with genetic and infectious diseases or cancer. For gene editing, his lab works on the design and selection of enzymes, known as nucleases, which include CRISPR/Cas. These enzymes function as molecular scissors that are capable of accurately disabling defective genes. By combining gene therapys ability to repair problem-causing genes and stem cells regenerative capabilities, he hopes to achieve cures of diseases as diverse as HIV, leukemia and brain cancer. He is also pioneering in vivo gene therapy approaches to make gene therapy and gene editing more broadly available and accessible to patients and those living with HIV, especially in resource-limited settings. He received his M.D. and Ph.D. at the University of Ulm, Germany.

Bruce Levine, Ph.D., Barbara and Edward Netter Professor in Cancer Gene Therapy is the Founding Director of the Clinical Cell and Vaccine Production Facility in the Department of Pathology and Laboratory Medicine and the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania. First-in-human adoptive immunotherapy trials include the first use of a lentiviral vector, the first infusions of gene edited cells, and the first use of lentivirally-modified cells to treat cancer. Dr. Levine has overseen the production, testing and release of 3,100 cellular products administered to more than 1,300 patients in clinical trials since 1996. Dr. Levine is a recipient of the William Osler Patient Oriented Research Award, the Wallace H. Coulter Award for Healthcare Innovation, the National Marrow Donor Program/Be The Match ONE Forum 2020 Dennis Confer Innovate Award, serves as President of the International Society for Cell and Gene Therapy, and on the Board of Directors of the Alliance for Regenerative Medicine. Dr. Levine received a B.A. in Biology from the University of Pennsylvania and a Ph.D. in Immunology and Infectious Diseases from Johns Hopkins University.

Peter Sage, Ph.D., is an Assistant Professor of Medicine at Harvard Medical School and an Associate Immunologist at Brigham and Womens Hospital. Dr. Sage is also a member of the Committee on Immunology (COI) at Harvard Medical School. Dr. Sage obtained his PhD in Immunology from Harvard Medical School in 2013, during which he received the Jeffrey Modell Prize. He completed a post-doctoral fellowship in the laboratory of Dr. Arlene Sharpe in the Department of Immunology at Harvard Medical School in 2017. Dr. Sage started his independent laboratory in 2017 at the Transplantation Research Center in the Division of Renal Medicine of Brigham and Womens Hospital. Dr. Sages laboratory focuses on studying how the immune system controls B cell and antibody responses in settings of health and disease.

About Immusoft

Immusoft is a cell therapy company focused on developing a novel therapies for rare diseases using a sustained delivery of protein therapeutics from a patients own cells. The company is developing a technology platform called Immune System Programming (ISP), which modifies a patients B cells and instructs the cells to produce gene-encoded medicines. The B cells that are reprogrammed using ISP become miniature drug factories that are expected to survive in patients for many years. The company is based in Seattle, WA. For more information, visit http://www.immusoft.com.

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Arrowhead Presents Positive Interim Clinical Data on ARO-HSD Treatment in Patients with Suspected NASH at EASL International Liver Congress – Business…

June 24th, 2021 1:54 am

PASADENA, Calif.--(BUSINESS WIRE)--Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today presented positive interim results from AROHSD1001, an ongoing Phase 1/2 clinical study of ARO-HSD, the companys investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with alcohol-related and nonalcohol related liver diseases, such as nonalcoholic steatohepatitis (NASH), at The International Liver Congress - The Annual Meeting of the European Association for the Study of the Liver (EASL). The data demonstrate that ARO-HSD is the first investigational therapeutic to achieve robust reductions in messenger RNA (mRNA) and protein levels of hepatic HSD17B13, leading to reductions in alanine aminotransferase (ALT), a liver enzyme typically elevated in liver diseases including NASH.

Javier San Martin, M.D., chief medical officer at Arrowhead, said: Genetic studies have recently shown that HSD17B13 is a compelling target for multiple forms of liver disease. It is exciting to present clinical data at EASL demonstrating that ARO-HSD is the first investigational medicine using any therapeutic modality to achieve inhibition of HSD17B13 in patients. It is also highly encouraging to see ALT levels drop significantly following just two doses of ARO-HSD. These data and the strong genetic evidence of HSD17B13 as a potential therapeutic target provide us with increased confidence as we consider the design of potential late-stage clinical studies for ARO-HSD.

Pharmacodynamics and Efficacy

All five patients with suspected NASH showed a strong pharmacodynamic effect as measured by liver biopsy at Day 71. HSD17B13 mRNA was reduced by a mean of 84%, with a range of 62-96%. HSD17B13 protein was reduced by 83% or greater. Two patients had a protein decrease of 92% and 97%, while the other three patients Day 71 measurements were reduced to below the lower limit of quantitation.

Mean ALT reduction from baseline was 46%, with all patients showing reductions ranging from 26-53%. ARO-HSD is the first investigational RNAi therapeutic to demonstrate robust inhibition of hepatic HSD17B13 mRNA and protein expression with associated reductions in ALT.

Safety and Tolerability

ARO-HSD was well tolerated without any identified safety signals in healthy volunteers given a single dose of ARO-HSD at 25mg, 50mg, 100mg or 200 mg and in the 5 patients with suspected NASH given a single 100 mg dose of ARO-HSD on Days 1 and 29. Adverse events were similar between subjects receiving ARO-HSD or placebo. Two instances of mild injection site bruising and mild injection site erythema were observed in ARO-HSD treated subjects. There were no ARO-HSD associated grade 3 or 4 laboratory abnormalities (NCI-CTCAE v5.0), no drug related serious or severe adverse events, and there were no drug discontinuations.

AROHSD1001 (NCT04202354) is a Phase 1/2 single and multiple dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of ARO-HSD in up to 74 normal healthy volunteers and patients with NASH or suspected NASH. Additional exploratory objectives include the assessment of various measures of drug activity using liver biopsy.

Presentation Details

Title: ARO-HSD reduces hepatic HSD17B13 mRNA expression and protein levels in patients with suspected NASHAuthors: Edward Gane, et al.Type: Late-Breaking PosterDate and Time: June 23, 2021 at 8:00 CEST

A copy of the presentation materials may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website. The abstract was also selected for inclusion in The International Liver Congress 2021 Official Scientific Press Conference: NAFLD/NASH on June 25, 2021.

HSD17B13 is a member of the hydroxysteroid dehydrogenase family involved in the metabolism of hormones, fatty acids, and bile acids. Published human genetic data indicate that a loss of function mutation in HSD17B13 provides strong protection against alcoholic hepatitis, cirrhosis, and NASH, with approximately 30-50% risk reduction compared to non-carriers.1

About Arrowhead Pharmaceuticals

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowheads RNAi-based therapeutics leverage this natural pathway of gene silencing.

For more information, please visit http://www.arrowheadpharma.com, or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadpharma.com/email-alerts.

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as may, will, expect, believe, anticipate, intend, plan, project, could, estimate, or continue are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.

Source: Arrowhead Pharmaceuticals, Inc.

________________

1 The New England Journal of Medicine. 2018, 1096-1106

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Pacific Biosciences and Rady Children’s Institute for Genomic Medicine Announce its First Research Collaboration for Whole – GlobeNewswire

June 24th, 2021 1:54 am

MENLO PARK, Calif., June 23, 2021 (GLOBE NEWSWIRE) -- Pacific Biosciences of California, Inc. (Nasdaq: PACB)(Pacific Biosciences or PacBio), a leading provider of high-quality, long-read sequencing platforms, and Rady Childrens Institute for Genomic Medicine (RCIGM), a mission-driven, non-profit seeking to save lives and improve outcomes for patients, clinicians and families, shared today that they are collaborating on a study which aims to identify potential disease-causing genetic variants and increase the solve rates of rare diseases.

The study is focused on long-read whole genome sequencing of rare disease cases for which previous short-read whole genome and exome sequencing yielded no answers. The study, which is currently underway, was able to detect variants that were not identified by short-read sequencing (SRS); of these, an average of 37 were missense mutations in known disease genes.

PacBio HiFi sequencing can identify numerous variants, both small and structural that are not readily detectable by SRS, said Matthew Bainbridge, Principal Investigator, and Associate Director of Clinical Genomics at RCIGM. We sequenced this cohort of patients to 10-30X depth of coverage using Pacific Biosciences HiFi long-read technology to assess whether there was an increase in the identification of these variants. We are very pleased by the preliminary results delivered in this collaboration with the team at PacBio.

It is estimated that as many as 25 million Americans approximately 1 in 13 people are affected by a rare, and often undiagnosed condition. In rare disease studies, conventional techniques for whole-genome and whole-exome analysis based on SRS typically led to identification of a causal variant in less than 50% of cases. Utilizing PacBios Single Molecule, Real-Time (SMRT) Sequencing technologyto generate highly accurate long-reads, known asHiFi reads,clinical researchers have demonstrated that they can detect disease-causing structural and small variants missed by short-read sequencing platforms. This study is designed to evaluate the rate at which HiFi sequencing identifies overlooked causal variation.

It is an honor to collaborate with the innovative pediatric translational researchers at RCIGM to bring HiFi Sequencing data to bear on some of their most difficult cases of rare pediatric disease, and hopefully give individuals and families answers regarding potential underlying genetic variants, which may ultimately provide healthcare providers with insights to end their diagnostic odysseys, said Christian Henry, CEO and President at PacBio.

Weve been aware that theres a subset of seriously ill babies and children who dont receive a diagnosis with current sequencing methods, but based on their symptoms, were fairly certain that they have an underpinning genetic disease, said Stephen Kingsmore, MD, DSc, President and CEO of Radys Childrens Institute for Genomic Medicine. With this new technology, we are excited to see how many more of these children and families will receive additional insight regarding the identification of potential disease-causing genetic variants.

About Pacific BiosciencesPacific Biosciences of California, Inc. (NASDAQ: PACB) is empowering life scientists with highly accurate long-read sequencing. The companys innovative instruments are based on Single Molecule, Real-Time (SMRT) Sequencing technology, which delivers a comprehensive view of genomes, transcriptomes, and epigenomes, enabling access to the full spectrum of genetic variation in any organism. Cited in thousands of peer-reviewed publications, PacBio sequencing systems are in use by scientists around the world to drive discovery in human biomedical research, plant and animal sciences, and microbiology. For more information, please visitwww.pacb.comand follow@PacBio.

About Rady Childrens Institute for Genomic MedicineWe are transforming pediatric critical care by advancing disease-specific healthcare for infants and children with rare disease. Discoveries at the Institute are enabling rapid diagnosis and targeted treatment of critically ill newborns and pediatric patients at Rady Childrens Hospital-San Diego and a growing network of more than 60 childrens hospitals nationwide. The vision is to expand delivery of this life-changing technology to enable the practice of Rapid Precision Medicine at childrens hospitals across the nation and the world. RCIGM is a non-profit, research institute of Rady Childrens Hospital and Health Center. Learn more at http://www.RadyGenomics.org. Follow us on Twitter and LinkedIn.

PacBio products are provided for Research Use Only. Not for use in diagnostic procedures.

Forward-Looking Statements This press release may contain forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the U.S. Private Securities Litigation Reform Act of 1995, including statements relating to the collaboration between PacBio and RCIGM, potential use of SMRT sequencing technology to identify, and increase the rate of identification of, potential disease-causing genetic variants in rare disease, the potential of HiFi data, the applications, insights, and attributes of SMRT sequencing technology, and the benefits of PacBio sequencing. Readers are cautioned not to place undue reliance on these forward-looking statements and any such forward-looking statements are qualified in their entirety by reference to the following cautionary statements. All forward-looking statements speak only as of the date of this press release and are based on current expectations and involve a number of assumptions, risks and uncertainties that could cause the actual results to differ materially from such forward-looking statements. Readers are strongly encouraged to read the full cautionary statements contained in the Companys filings with the Securities and Exchange Commission, including the risks set forth in the companys Forms 8-K, 10-K, and 10-Q. The Company disclaims any obligation to update or revise any forward-looking statements.

Contacts

Investors:Todd Friedman+1 (650) 521-8450ir@pacificbiosciences.com

Media:Jen Carroll+1 (858) 449-8082pr@pacificbiosciences.com

Grace Sevilla+1 858-966-1710 (o); +1 619-855-5135 cell (c)gsevilla@rchsd.org

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Pacific Biosciences and Rady Children's Institute for Genomic Medicine Announce its First Research Collaboration for Whole - GlobeNewswire

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Despite the challenges of COVID-19, Yale-PCCSM section members continued their work on scientific papers – Yale School of Medicine

June 24th, 2021 1:54 am

Despite the challenges of COVID-19, Yale Pulmonary, Critical Care & Sleep Medicine (Yale-PCCSM) section members at Yale School of Medicine (YSM) continued their work on scientific papers. Here is a list of their recent original research papers in which either the first or last author is a Yale-PCCSM section member. Hannah Oakland and Jacqueline Geer are fellows.

Nucleotide-binding domain and leucine-rich-repeat-containing protein X1 deficiency induces nicotinamide adenine dinucleotide decline, mechanistic target of rapamycin activation, and cellular senescence and accelerates aging lung-like changes. Shin HJ, Kim SH, Park HJ, Shin MS, Kang I, Kang MJ. Aging Cell. 2021 Jun 4; 2021 Jun 4. PMID: 34087956.

Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis. Vukmirovic M, Yan X, Gibson KF, Gulati M, Schupp JC, DeIuliis G, Adams TS, Hu B, Mihaljinec A, Woolard TN, Lynn H, Emeagwali N, Herzog EL, Chen ES, Morris A, Leader JK, Zhang Y, Garcia JGN, Maier LA, Collman RG, Drake WP, Becich MJ, Hochheiser H, Wisniewski SR, Benos PV, Moller DR, Prasse A, Koth LL, Kaminski N. Eur Respir J. 2021 Jun 3; 2021 Jun 3. PMID: 34083402.

Functional Effects of Intervening Illnesses and Injuries After Critical Illness in Older Persons. Gill TM, Han L, Gahbauer EA, Leo-Summers L, Murphy TE, Ferrante LE. Crit Care Med. 2021 Jun 1. PMID: 33497167.

The Arterial Load and Right Ventricular-Vascular Coupling in Pulmonary Hypertension. Oakland HT, Joseph P, Naeije R, Elassal A, Cullinan M, Heerdt PM, Singh I. J Appl Physiol (1985). 2021 May 27; 2021 May 27. PMID: 34043473.

Integrated Single Cell Atlas of Endothelial Cells of the Human Lung. Schupp JC, Adams TS, Cosme C Jr, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, DeIuliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich NE, Kropski JA, Niklason LE, Pe'er D, Yan X, Homer RJ, Rosas IO, Kaminski N. Circulation. 2021 May 25; 2021 May 25. PMID: 34030460.

G2S3: A gene graph-based imputation method for single-cell RNA sequencing data. Wu W, Liu Y, Dai Q, Yan X, Wang Z. PLoS Comput Biol. 2021 May 18; 2021 May 18. PMID: 34003861.

Surveillance of adverse drug events associated with tocilizumab in hospitalized veterans with coronavirus disease 2019 (COVID-19) to inform patient safety and pandemic preparedness. Datta R, Barrett A, Burk M, Salone C, Au A, Cunningham F, Fisher A, Dembry LM, Akgn KM. Infect Control Hosp Epidemiol. 2021 May 14; 2021 May 14. PMID: 33985598.

SPLUNC1: a novel marker of cystic fibrosis exacerbations. Khanal S, Webster M, Niu N, Zielonka J, Nunez M, Chupp G, Slade MD, Cohn L, Sauler M, Gomez JL, Tarran R, Sharma L, Dela Cruz CS, Egan M, Laguna T, Britto CJ. Eur Respir J. 2021 May 6; 2021 May 6. PMID: 33958427.

PINK1 Inhibits Multimeric Aggregation and Signaling of MAVS and MAVS-Dependent Lung Pathology. Kim SH, Shin HJ, Yoon CM, Lee SW, Sharma L, Dela Cruz CS, Kang MJ. Am J Respir Cell Mol Biol. 2021 May. PMID: 33577398.

Obstructive Sleep Apnea as a Risk Factor for Intracerebral Hemorrhage. Geer JH, Falcone GJ, Vanent KN, Leasure AC, Woo D, Molano JR, Sansing LH, Langefeld CD, Pisani MA, Yaggi HK, Sheth KN. Stroke. 2021 May; 2021 Apr 8. PMID: 33827242.

Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma. Chen A, Diaz-Soto MP, Sanmamed MF, Adams T, Schupp JC, Gupta A, Britto C, Sauler M, Yan X, Liu Q, Nino G, Cruz CSD, Chupp GL, Gomez JL. Respir Res. 2021 Apr 26; 2021 Apr 26. PMID: 33902571.

Mitochondrial antiviral signaling protein is crucial for the development of pulmonary fibrosis. Kim SH, Lee JY, Yoon CM, Shin HJ, Lee SW, Rosas I, Herzog E, Dela Cruz CS, Kaminski N, Kang MJ. Eur Respir J. 2021 Apr; 2021 Apr 15. PMID: 33093124.

Elevated IL-15 concentrations in the sarcoidosis lung is independent of granuloma burden and disease phenotypes. Minasyan M, Sharma L, Pivarnik T, Liu W, Adams T, Bermejo S, Peng X, Liu A, Ishikawa G, Perry C, Kaminski N, Gulati M, Herzog EL, Dela Cruz CS, Ryu C. Am J Physiol Lung Cell Mol Physiol. 2021 Apr 14; 2021 Apr 14. PMID: 33851886.

Randomized trial of physical activity on quality of life and lung cancer biomarkers in patients with advanced stage lung cancer: a pilot study. Bade BC, Gan G, Li F, Lu L, Tanoue L, Silvestri GA, Irwin ML. BMC Cancer. 2021 Apr 1; 2021 Apr 1. PMID: 33794808.

Added Diagnostic Utility of Clinical Metagenomics for the Diagnosis of Pneumonia in Immunocompromised Adults. Azar MM, Schlaberg R, Malinis MF, Bermejo S, Schwarz T, Xie H, Dela Cruz CS. Chest. 2021 Apr; 2020 Nov 18. PMID: 33217418.

The Association Between Hospital End-of-Life Care Quality and the Care Received Among Patients With Heart Failure. Feder SL, Tate J, Ersek M, Krishnan S, Chaudhry SI, Bastian LA, Rolnick J, Kutney-Lee A, Akgn KM. J Pain Symptom Manage. 2021 Apr; 2020 Sep 12. PMID: 32931904.

Reviews/editorials

Genetic Variants of SARS-CoV-2: What do we know so far? Jamil S, Shafazand S, Pasnick S, Carlos WG, Maves R, Dela Cruz C. Am J Respir Crit Care Med. 2021 May 10; 2021 May 10. PMID: 33970826.

Sleep during lockdown. Kryger MH. Sleep Health. 2021 May 8; 2021 May 8. PMID: 33975818.

Showing a dream. Kryger MH. Sleep Health. 2021 Apr; 2021 Mar 5. PMID: 33685831

2020 Updated Asthma Guidelines: Bronchial thermoplasty in the management of asthma. Castro M, Chupp G. J Allergy Clin Immunol. 2021 May; 2021 Mar 2. PMID: 33667476.

The Section of Pulmonary, Critical Care and Sleep Medicine is one of the eleven sections within YSMs Department of Internal Medicine. To learn more about Yale-PCCSM, visit PCCSMs website, or follow them on Facebook and Twitter.

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Despite the challenges of COVID-19, Yale-PCCSM section members continued their work on scientific papers - Yale School of Medicine

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Veritas Intercontinental: Genetics makes it possible to identify cardiovascular genetic risk and prevent cardiac accidents such as those that have…

June 24th, 2021 1:54 am

MADRID, June 22, 2021 /PRNewswire/ -- We have recently witnessed, once again, a professional athlete suffering a cardiovascular attack during a match. This type of incidence and the possible fatal consequences result from an individual's genetic makeup. Genetic science now makes it possible to know whether a person has an elevated risk to suffer this type of cardiovascular accident and to avoid one of the main causes of death in the world, with more than 17 million deaths each year.

The role of genetics as a diagnostic element has been fundamental for several years, as Dr. Izquierdo, Chief Medical Officer of Veritas Intercontinental, says: "Sudden cardiac death (SCD) is mainly due to coronary pathologies, especially in patients over 40 years old, but in younger patients, such as many high-performance professional athletes, the contribution of genetic factors to the pathogenesis of SCD is a key factor, since we usually find a clear pattern of family inheritance at its origin, such as cardiomyopathies or channelopathies".

To help in the detection and prevention of Cardio Vascular Disease (CVD), Veritas Intercontinental offers the myCardiogenetic service, an innovative Exome sequencing and interpretation service, focused on genes related to hereditary heart diseases.

The analysis includes all genes recommended by the American Heart Association (AHA) analyzing 100 genes based on their relationship with different hereditary heart diseases. The service includes genetic counseling for the prescribing specialist, which is essential for the correct interpretation of the results and clinical management of the patient.

"myCardio,"explains Dr. Luis Izquierdo, "makes it possible to tackle the main types of cardiac disorders of hereditary origin and offers enormously valuable information to avoid the disease or to treat it much more efficiently. Until now, genetic tests related to hereditary heart disease have been very focused on certain pathologies, when it has been shown that there are many interactions between different heart conditions. myCardio allows a comprehensive approach to heart disease, with a new perspective that has been shown to be much more effective".

Advantages

Whole exome sequencing (WES) is the most appropriate tool to address the genetic heterogeneity present in inherited cardiovascular disease. Recent studies show a very significant improvement in diagnostic performance using exome sequencing compared to panels, since a high number of cases in which several mutations are recorded simultaneously are observed. The advantages of the exome are more prominent in those cases in which there is no high clinical suspicion, as well as those in which the patient has been recovered after an episode of sudden death.

The service covers the study of hereditary predisposition to Primary Cardiomyopathies, Metabolic Cardiomyopathies, Channelopathies and Arrhythmias, Syndromes with Vascular Affection, Rasopathies,other syndromes linked to cardiac pathology and other risk factors (Ischemic Heart Disease) such as Familial Hypercholesterolemia.

About Veritas Intercontinental

Veritas Intercontinental was founded in 2018 by Dr. Luis Izquierdo, Dr. Vincenzo Cirigliano and Javier de Echevarra, who have accumulated extensive experience in the field of genetics, diagnostics, and biotechnology, initially linked to Veritas Genetics, a company founded in 2014 by Prof. George Church, one of the pioneers in preventive medicine. Veritas was born with the aim of making genome sequencing and its clinical interpretation available to all citizens as a tool to prevent diseases and improve health and quality of life.

Since its inception, Veritas Intercontinental has led the activity and development of the Veritas market in Europe, Latin America, the Middle East, and Japan; with the aim of making genomics an everyday tool used for proactive healthcare management.

Based on its leadership in the application of preventive genomic medicine (myGenome), Veritas Intercontinental has expanded its offer to other areas such as perinatal medicine (myPrenatal -NIPT- and myNewborn -neonatal screening-), oncology (myCancerRisk), or the mentioned cardiovascular pathologies (myCardio), thus becoming the benchmark in advanced genomics services.

For further informationhttps://www.veritasint.com

Marta Pereiro[emailprotected]+34 915 623 675

Logo - https://mma.prnewswire.com/media/876462/Veritas_Intercontinental_Logo.jpg

SOURCE Veritas Intercontinental

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New Research Uncovers How Cancers with Common Gene Mutation Develop Resistance to Targeted Drugs – Newswise

June 24th, 2021 1:54 am

Newswise A new study by Dana-Farber Cancer Institute researchers has given scientists their first look at the genomic landscape of tumors that have grown resistant to drugs targeting the abnormal KRASG12C protein. Their work shows that, far from adopting a common route to becoming resistant, the cells take a strikingly diverse set of avenues, often several at a time.

The findings, reported online today in the New England Journal of Medicine, underscore the need for new drugs that inhibit KRAS differently than current agents do. And, because resistance can arise through many different mechanisms, effective treatment for these cancers will likely require combinations of KRAS inhibitors and other targeted drugs.

Mutations in the KRAS gene are fairly common across cancer types, said Dana-Farbers Mark Awad, MD, PhD, the co-first author of the paper with Shengwu Liu, PhD, also of Dana-Farber. The particular mutation we focused on in this study, KRASG12C, is found in about 13% of non-small cell lung cancers [NSCLC], where its often associated with tobacco use, in up to 3% of colorectal cancers, and less frequently in a range of other cancers. While no targeted therapy has been approved for this specific molecular subtype, two inhibitors of the KRASG12C protein adagrasib and sotorasib have shown promise in clinical trials, especially in patients with NSCLC.

While results from these early clinical trials are encouraging, the cancer usually becomes resistant to these drugs, Awad continued. The mechanisms of resistance the genomic and other changes that occur that allow the cancer to begin growing again are largely unknown. This study sought to identify them.

In a multi-institutional effort, researchers collected tumor samples from 38 patients with cancers carrying KRASG12C mutations 27 with NSCLC, 10 with colorectal cancer, and one with cancer of the appendix. Analysis of the samples uncovered possible causes of resistance to adagrasib in 17 of the patients, seven of whom had multiple causes.

The resistance mechanisms fell into three categories:

The number of patients with KRAS alterations and non-KRAS genetic abnormalities was roughly equal, and many patients had both types of resistance mechanisms.

The effort to uncover KRAS mutations associated with drug resistance was also led by the studys senior author, Andrew Aguirre, MD, PhD, of Dana-Farber, Brigham and Womens Hospital, and the Broad Institute of MIT and Harvard. Aguirre and his colleagues created a series of cell lines, each containing the G12C mutation plus an additional mutation elsewhere in the KRAS gene. The set represented every possible second mutation in KRASG12C that would give rise to an abnormal protein. The researchers then ran tests to see which of the doubly mutated genes gave cells the ability to become resistant to sotorasib or an adagrasib-like compound. They also tested the further-mutated versions of KRASG12C that the team had identified in patients.

They found that some of the new mutations conferred resistance to both agents, whereas others provided resistance to just one.

In addition to identifying resistance mutations that have already occurred in patients receiving adagrasib, our study also provides an atlas of all possible mutations in KRASG12C that can cause resistance to adagrasib and/or sotorasib, Aguirre said. These results will be a valuable resource for oncologists to interpret future acquired mutations that occur in patients who become resistant to these drugs and may be used to guide the choice of which KRASG12C inhibitor is right for each patient.

The study results point to the variety of ways cancers with KRASG12C mutations can overcome the effects of adagrasib, the authors say. Cancers with the KRASG12C mutation constitute a large proportion of all lung cancers, and many pharmaceutical companies are developing KRASG12C inhibitors, Awad observed. The hope is that studies such as this, which uncover resistance mechanisms, will help drive future studies of combination therapies to delay or prevent resistance or overcome it when it occurs.

The study co-authors are Julien Dilly, MS, Joseph O. Jacobson, MD, MSc, Kristen E. Lowder, Hanrong Feng, MA, Brian M. Wolpin, MD, MPH, and Pasi A. Jnne, MD, PhD, of Dana-Farber; Kevin M. Haigis, PhD, of Dana-Farber and the Broad Institute; Igor I. Rybkin, MD, PhD, of Henry Ford Cancer Institute; Kathryn C. Arbour, MD, Gregory J. Riely, MD, PhD, and Piro Lito, MD, PhD, of Memorial Sloan Kettering Cancer Institute; Viola W. Zhu, MD, PhD, Shannon S. Zhang, MD, and Sai-Hong Ignatius Ou, MD, PhD, of the University of California Irvine; Melissa L. Johnson, MD, of Sarah Cannon Research Institute; Rebecca S. Heist, MD, MPH, and Yin P. Hung, MD, PhD, of Massachusetts General Hospital; Tejas Patil, MD, of the University of Colorado; Xiaoping Yang, PhD, Nicole S. Persky, PhD, and David E. Root, PhD, of the Broad Institute; Lynette M. Sholl, MD, of BWH; Julie Wiese, and Jason Christiansen, PhD, of Boundless Bio, La Jolla, Calif.; Jessica Lee, MS, and Alexa B. Schrock, PhD, of Foundation Medicine, Cambridge, Mass.; Lee P. Lim, PhD, Kavita Garg, PhD, and Mark Li, of Resolution Bioscience, Kirkland, Wash.; and Lars D. Engstrom, Laura Waters, MS, J. David Lawson, PhD, Peter Olson, PhD, and James G. Christensen, PhD, of Mirati Therapeutics, San Diego, Calif.

The research was funded by Mirati Therapeutics; the Lustgarten Foundation; the Dana-Farber Cancer Institute Hale Center for Pancreatic Cancer Research; the National Cancer Institute (grants KO8CA218420-02, P50CA127003, U01CA20171, 1R01CA230745-01, and 1R01CA230267-01A1); Stand Up to Cancer; the Pancreatic Cancer Action Network; the Noble Effort Fund; the Wexler Family Fund; Promises for Purple; the Bob Parsons Fund; the Pew Charitable Trusts; the Damon Runyon Cancer Research Foundation; the Josie Robertson Investigator Program at Memorial Sloan Kettering; the Mark Foundation for Cancer Research; and the American Cancer Society.

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New Research Uncovers How Cancers with Common Gene Mutation Develop Resistance to Targeted Drugs - Newswise

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Diabetes – Wikipedia

June 24th, 2021 1:53 am

Group of metabolic disorders

Medical condition

Diabetes mellitus (DM), commonly known as just diabetes, is a group of metabolic disorders characterized by a high blood sugar level over a prolonged period of time.[11] Symptoms often include frequent urination, increased thirst and increased appetite.[2] If left untreated, diabetes can cause many health complications.[2] Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death.[3] Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, damage to the nerves, damage to the eyes and cognitive impairment.[2][5]

Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced.[12] There are three main types of diabetes mellitus:[2]

Type 1 diabetes must be managed with insulin injections.[2] Prevention and treatment of type 2 diabetes involves maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco.[2] Type 2 diabetes may be treated with medications such as insulin sensitizers with or without insulin.[15] Control of blood pressure and maintaining proper foot and eye care are important for people with the disease.[2] Insulin and some oral medications can cause low blood sugar.[16] Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 diabetes.[17] Gestational diabetes usually resolves after the birth of the baby.[18]

As of 2019[update], an estimated 463million people had diabetes worldwide (8.8% of the adult population), with type 2 diabetes making up about 90% of the cases.[10] Rates are similar in women and men.[19] Trends suggest that rates will continue to rise.[10] Diabetes at least doubles a person's risk of early death.[2] In 2019, diabetes resulted in approximately 4.2million deaths.[10] It is the 7th leading cause of death globally.[20][21] The global economic cost of diabetes-related health expenditure in 2017 was estimated at US$727 billion.[10] In the United States, diabetes cost nearly US$327billion in 2017.[22] Average medical expenditures among people with diabetes are about 2.3 times higher.[23]

The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger).[24] Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes.[25]

Several other signs and symptoms can mark the onset of diabetes although they are not specific to the disease. In addition to the known symptoms listed above, they include blurred vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Long-term vision loss can also be caused by diabetic retinopathy. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.[26]

People with diabetes (usually but not exclusively in type 1 diabetes) may also experience diabetic ketoacidosis (DKA), a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness. DKA requires emergency treatment in hospital.[27] A rarer but more dangerous condition is hyperosmolar hyperglycemic state (HHS), which is more common in type 2 diabetes and is mainly the result of dehydration caused by high blood sugars.[27]

Treatment-related low blood sugar (hypoglycemia) is common in people with type 1 and also type 2 diabetes depending on the medication being used. Most cases are mild and are not considered medical emergencies. Effects can range from feelings of unease, sweating, trembling, and increased appetite in mild cases to more serious effects such as confusion, changes in behavior such as aggressiveness, seizures, unconsciousness, and rarely permanent brain damage or death in severe cases.[28][29] Rapid breathing, sweating, and cold, pale skin are characteristic of low blood sugar but not definitive.[30] Mild to moderate cases are self-treated by eating or drinking something high in rapidly absorbed carbohydrates. Severe cases can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.[31]

All forms of diabetes increase the risk of long-term complications. These typically develop after many years (1020) but may be the first symptom in those who have otherwise not received a diagnosis before that time.

The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease[32] and about 75% of deaths in people with diabetes are due to coronary artery disease.[33] Other macrovascular diseases include stroke, and peripheral artery disease.

The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves.[34] Damage to the eyes, known as diabetic retinopathy, is caused by damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and eventual blindness.[34] Diabetes also increases the risk of having glaucoma, cataracts, and other eye problems. It is recommended that people with diabetes visit an eye doctor once a year.[35] Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplantation.[34] Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes.[34] The symptoms can include numbness, tingling, pain, and altered pain sensation, which can lead to damage to the skin. Diabetes-related foot problems (such as diabetic foot ulcers) may occur, and can be difficult to treat, occasionally requiring amputation. Additionally, proximal diabetic neuropathy causes painful muscle atrophy and weakness.

There is a link between cognitive deficit and diabetes. Compared to those without diabetes, those with the disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function.[36] Having diabetes, especially when on insulin, increases the risk of falls in older people.[37]

Diabetes mellitus is classified into six categories: type 1 diabetes, type 2 diabetes, hybrid forms of diabetes, hyperglycemia first detected during pregnancy, "unclassified diabetes", and "other specific types".[40] The "hybrid forms of diabetes" contains slowly evolving, immune-mediated diabetes of adults and ketosis-prone type 2 diabetes. The "hyperglycemia first detected during pregnancy" contains gestational diabetes mellitus and diabetes mellitus in pregnancy (type 1 or type 2 diabetes first diagnosed during pregnancy). The "other specific types" are a collection of a few dozen individual causes. Diabetes is a more variable disease than once thought and people may have combinations of forms.[41] The term "diabetes", without qualification, refers to diabetes mellitus.[42]

Type1 diabetes is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type1 diabetes is of an immune-mediated nature, in which a T cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin.[43] It causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Although it has been called "juvenile diabetes" due to the frequent onset in children, the majority of individuals living with type 1 diabetes are now adults.[6]

"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used.[44] Still, type1 diabetes can be accompanied by irregular and unpredictable high blood sugar levels, and the potential for diabetic ketoacidosis or serious low blood sugar levels. Other complications include an impaired counterregulatory response to low blood sugar, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease).[44] These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type1 diabetes.[45]

Type1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors,[46] such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans.[46][47] Among dietary factors, data suggest that gliadin (a protein present in gluten) may play a role in the development of type 1 diabetes, but the mechanism is not fully understood.[48][49]

Type 1 diabetes can occur at any age, and a significant proportion is diagnosed during adulthood. Latent autoimmune diabetes of adults (LADA) is the diagnostic term applied when type 1 diabetes develops in adults; it has a slower onset than the same condition in children. Given this difference, some use the unofficial term "type 1.5 diabetes" for this condition. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes, based on age rather than a cause.[50]

Type 2 diabetes is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion.[12] The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type of diabetes mellitus.[2] Many people with type 2 diabetes have evidence of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) before meeting the criteria for type 2 diabetes.[51] The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by lifestyle changes or medications that improve insulin sensitivity or reduce the liver's glucose production.[52]

Type 2 diabetes is primarily due to lifestyle factors and genetics.[53] A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than 30), lack of physical activity, poor diet, stress, and urbanization.[38] Excess body fat is associated with 30% of cases in people of Chinese and Japanese descent, 6080% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders.[12] Even those who are not obese may have a high waisthip ratio.[12]

Dietary factors such as sugar-sweetened drinks are associated with an increased risk.[54][55] The type of fats in the diet is also important, with saturated fat and trans fats increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk.[53] Eating white rice excessively may increase the risk of diabetes, especially in Chinese and Japanese people.[56] Lack of physical activity may increase the risk of diabetes in some people.[57]

Adverse childhood experiences (ACEs), including abuse, neglect, and household difficulties, increase the likelihood of type 2 diabetes later in life by 32%, with neglect having the strongest effect.[58]

Gestational diabetes resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 210% of all pregnancies and may improve or disappear after delivery.[59] It is recommended that all pregnant women get tested starting around 2428 weeks gestation.[60] It is most often diagnosed in the second or third trimester because of the increase in insulin-antagonist hormone levels that occurs at this time.[60] However, after pregnancy approximately 510% of women with gestational diabetes are found to have another form of diabetes, most commonly type 2.[59] Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. Management may include dietary changes, blood glucose monitoring, and in some cases, insulin may be required.[61]

Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital heart and central nervous system abnormalities, and skeletal muscle malformations. Increased levels of insulin in a fetus's blood may inhibit fetal surfactant production and cause infant respiratory distress syndrome. A high blood bilirubin level may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.[62]

Maturity onset diabetes of the young (MODY) is a rare autosomal dominant inherited form of diabetes, due to one of several single-gene mutations causing defects in insulin production.[63] It is significantly less common than the three main types, constituting 12% of all cases. The name of this disease refers to early hypotheses as to its nature. Being due to a defective gene, this disease varies in age at presentation and in severity according to the specific gene defect; thus there are at least 13 subtypes of MODY. People with MODY often can control it without using insulin.[64]

Some cases of diabetes are caused by the body's tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells, whereas others increase insulin resistance (especially glucocorticoids which can provoke "steroid diabetes"). The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (MRDM or MMDM, ICD-10 code E12), was deprecated by the World Health Organization (WHO) when the current taxonomy was introduced in 1999.[65]Yet another form of diabetes that people may develop is double diabetes. This is when a type 1 diabetic becomes insulin resistant, the hallmark for type 2 diabetes or has a family history for type 2 diabetes.[66] It was first discovered in 1990 or 1991.

The following is a list of disorders that may increase the risk of diabetes:[67]

Insulin is the principal hormone that regulates the uptake of glucose from the blood into most cells of the body, especially liver, adipose tissue and muscle, except smooth muscle, in which insulin acts via the IGF-1.[citation needed] Therefore, deficiency of insulin or the insensitivity of its receptors play a central role in all forms of diabetes mellitus.[69]

The body obtains glucose from three main sources: the intestinal absorption of food; the breakdown of glycogen (glycogenolysis), the storage form of glucose found in the liver; and gluconeogenesis, the generation of glucose from non-carbohydrate substrates in the body.[70] Insulin plays a critical role in regulating glucose levels in the body. Insulin can inhibit the breakdown of glycogen or the process of gluconeogenesis, it can stimulate the transport of glucose into fat and muscle cells, and it can stimulate the storage of glucose in the form of glycogen.[70]

Insulin is released into the blood by beta cells (-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Lower glucose levels result in decreased insulin release from the beta cells and in the breakdown of glycogen to glucose. This process is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin.[71]

If the amount of insulin available is insufficient, or if cells respond poorly to the effects of insulin (insulin resistance), or if the insulin itself is defective, then glucose is not absorbed properly by the body cells that require it, and is not stored appropriately in the liver and muscles. The net effect is persistently high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as metabolic acidosis in cases of complete insulin deficiency.[70]

When glucose concentration in the blood remains high over time, the kidneys reach a threshold of reabsorption, and the body excretes glucose in the urine (glycosuria).[72] This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume is replaced osmotically from water in body cells and other body compartments, causing dehydration and increased thirst (polydipsia).[70] In addition, intracellular glucose deficiency stimulates appetite leading to excessive food intake (polyphagia).[73]

Diabetes mellitus is diagnosed with a test for the glucose content in the blood, and is diagnosed by demonstrating any one of the following:[65]

A positive result, in the absence of unequivocal high blood sugar, should be confirmed by a repeat of any of the above methods on a different day. It is preferable to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test.[77] According to the current definition, two fasting glucose measurements above 7.0mmol/L (126mg/dL) is considered diagnostic for diabetes mellitus.

Per the WHO, people with fasting glucose levels from 6.1 to 6.9mmol/L (110 to 125mg/dL) are considered to have impaired fasting glucose.[78] People with plasma glucose at or above 7.8mmol/L (140mg/dL), but not over 11.1mmol/L (200mg/dL), two hours after a 75gram oral glucose load are considered to have impaired glucose tolerance. Of these two prediabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus, as well as cardiovascular disease.[79] The American Diabetes Association (ADA) since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to 6.9mmol/L (100 to 125mg/dL).[80]

Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.[81]

There is no known preventive measure for type1 diabetes.[2] Type2 diabeteswhich accounts for 8590% of all cases worldwidecan often be prevented or delayed[82] by maintaining a normal body weight, engaging in physical activity, and eating a healthy diet.[2] Higher levels of physical activity (more than 90 minutes per day) reduce the risk of diabetes by 28%.[83] Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts, vegetable oils, and fish.[84] Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help prevent diabetes.[84] Tobacco smoking is also associated with an increased risk of diabetes and its complications, so smoking cessation can be an important preventive measure as well.[85]

The relationship between type 2 diabetes and the main modifiable risk factors (excess weight, unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world. There is growing evidence that the underlying determinants of diabetes are a reflection of the major forces driving social, economic and cultural change: globalization, urbanization, population aging, and the general health policy environment.[86]

Diabetes management concentrates on keeping blood sugar levels as close to normal, without causing low blood sugar. This can usually be accomplished with dietary changes, exercise, weight loss, and use of appropriate medications (insulin, oral medications).

Learning about the disease and actively participating in the treatment is important, since complications are far less common and less severe in people who have well-managed blood sugar levels.[87][88] Per the American College of Physicians, the goal of treatment is an HbA1C level of 7-8%.[89] Attention is also paid to other health problems that may accelerate the negative effects of diabetes. These include smoking, high blood pressure, metabolic syndrome obesity, and lack of regular exercise.[90] Specialized footwear is widely used to reduce the risk of ulcers in at-risk diabetic feet although evidence for the efficacy of this remains equivocal.[91]

People with diabetes can benefit from education about the disease and treatment, dietary changes, and exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.[92][93]

Weight loss can prevent progression from prediabetes to diabetes type 2, decrease the risk of cardiovascular disease, or result in a partial remission in people with diabetes.[94][95] No single dietary pattern is best for all people with diabetes.[96] Healthy dietary patterns, such as the Mediterranean diet, low-carbohydrate diet, or DASH diet, are often recommended, although evidence does not support one over the others.[94][95] According to the ADA, "reducing overall carbohydrate intake for individuals with diabetes has demonstrated the most evidence for improving glycemia", and for individuals with type 2 diabetes who cannot meet the glycemic targets or where reducing anti-glycemic medications is a priority, low or very-low carbohydrate diets are a viable approach.[95] For overweight people with type 2 diabetes, any diet that achieves weight loss is effective.[96][97]

Most medications used to treat diabetes act by lowering blood sugar levels through different mechanisms. There is broad consensus that when people with diabetes maintain tight glucose control keeping the glucose levels in their blood within normal ranges they experience fewer complications, such as kidney problems or eye problems.[98][99] There is however debate as to whether this is appropriate and cost effective for people later in life in whom the risk of hypoglycemia may be more significant.[100]

There are a number of different classes of anti-diabetic medications. Type1 diabetes requires treatment with insulin, ideally using a "basal bolus" regimen that most closely matches normal insulin release: long-acting insulin for the basal rate and short-acting insulin with meals.[101] Type 2 diabetes is generally taken with medication that is taken by mouth (e.g. metformin) although some eventually require injectable treatment with insulin or GLP-1 agonists.[102]

Metformin is generally recommended as a first-line treatment for type2 diabetes, as there is good evidence that it decreases mortality.[8] It works by decreasing the liver's production of glucose.[103] Several other groups of drugs, mostly given by mouth, may also decrease blood sugar in type 2 diabetes. These include agents that increase insulin release (sulfonylureas), agents that decrease absorption of sugar from the intestines (acarbose), agents that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4) that inactivates incretins such as GLP-1 and GIP (sitagliptin), agents that make the body more sensitive to insulin (thiazolidinedione) and agents that increase the excretion of glucose in the urine (SGLT2 inhibitors).[103] When insulin is used in type2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications.[8] Doses of insulin are then increased until glucose targets are reached.[8][104]

Cardiovascular disease is a serious complication associated with diabetes, and many international guidelines recommend blood pressure treatment targets that are lower than 140/90mmHg for people with diabetes.[105] However, there is only limited evidence regarding what the lower targets should be. A 2016 systematic review found potential harm to treating to targets lower than 140 mmHg,[106] and a subsequent systematic review in 2019 found no evidence of additional benefit from blood pressure lowering to between 130 - 140mmHg, although there was an increased risk of adverse events.[107]

2015 American Diabetes Association recommendations are that people with diabetes and albuminuria should receive an inhibitor of the renin-angiotensin system to reduce the risks of progression to end-stage renal disease, cardiovascular events, and death.[108] There is some evidence that angiotensin converting enzyme inhibitors (ACEIs) are superior to other inhibitors of the renin-angiotensin system such as angiotensin receptor blockers (ARBs),[109] or aliskiren in preventing cardiovascular disease.[110] Although a more recent review found similar effects of ACEIs and ARBs on major cardiovascular and renal outcomes.[111] There is no evidence that combining ACEIs and ARBs provides additional benefits.[111]

The use of aspirin to prevent cardiovascular disease in diabetes is controversial.[108] Aspirin is recommended by some in people at high risk of cardiovascular disease, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes.[112] 2015 American Diabetes Association recommendations for aspirin use (based on expert consensus or clinical experience) are that low-dose aspirin use is reasonable in adults with diabetes who are at intermediate risk of cardiovascular disease (10-year cardiovascular disease risk, 510%).[108] National guidelines for England and Wales by the National Institute for Health and Care Excellence (NICE) recommend against the use of aspirin in people with type 1 or type 2 diabetes who do not have confirmed cardiovascular disease.[101][102]

Weight loss surgery in those with obesity and type 2 diabetes is often an effective measure.[17] Many are able to maintain normal blood sugar levels with little or no medications following surgery[113] and long-term mortality is decreased.[114] There is, however, a short-term mortality risk of less than 1% from the surgery.[115] The body mass index cutoffs for when surgery is appropriate are not yet clear.[114] It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.[116]

A pancreas transplant is occasionally considered for people with type1 diabetes who have severe complications of their disease, including end stage kidney disease requiring kidney transplantation.[117]

In countries using a general practitioner system, such as the United Kingdom, care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care in a team approach. Home telehealth support can be an effective management technique.[118]

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In 2017, 425million people had diabetes worldwide,[119] up from an estimated 382million people in 2013[120] and from 108million in 1980.[121] Accounting for the shifting age structure of the global population, the prevalence of diabetes is 8.8% among adults, nearly double the rate of 4.7% in 1980.[119][121] Type2 makes up about 90% of the cases.[19][38] Some data indicate rates are roughly equal in women and men,[19] but male excess in diabetes has been found in many populations with higher type 2 incidence, possibly due to sex-related differences in insulin sensitivity, consequences of obesity and regional body fat deposition, and other contributing factors such as high blood pressure, tobacco smoking, and alcohol intake.[122][123]

The WHO estimates that diabetes resulted in 1.5million deaths in 2012, making it the 8th leading cause of death.[15][121] However another 2.2million deaths worldwide were attributable to high blood glucose and the increased risks of cardiovascular disease and other associated complications (e.g. kidney failure), which often lead to premature death and are often listed as the underlying cause on death certificates rather than diabetes.[121][124] For example, in 2017, the International Diabetes Federation (IDF) estimated that diabetes resulted in 4.0million deaths worldwide,[119] using modeling to estimate the total number of deaths that could be directly or indirectly attributed to diabetes.[119]

Diabetes occurs throughout the world but is more common (especially type 2) in more developed countries. The greatest increase in rates has however been seen in low- and middle-income countries,[121] where more than 80% of diabetic deaths occur.[125] The fastest prevalence increase is expected to occur in Asia and Africa, where most people with diabetes will probably live in 2030.[126] The increase in rates in developing countries follows the trend of urbanization and lifestyle changes, including increasingly sedentary lifestyles, less physically demanding work and the global nutrition transition, marked by increased intake of foods that are high energy-dense but nutrient-poor (often high in sugar and saturated fats, sometimes referred to as the "Western-style" diet).[121][126] The global number of diabetes cases might increase by 48% between 2017 and 2045.[119]

Diabetes was one of the first diseases described,[127] with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine."[128] The Ebers papyrus includes a recommendation for a drink to take in such cases.[129] The first described cases are believed to have been type1 diabetes.[128] Indian physicians around the same time identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants.[128][129]

The term "diabetes" or "to pass through" was first used in 230BCE by the Greek Apollonius of Memphis.[128] The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career.[128] This is possibly due to the diet and lifestyle of the ancients, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa).[130]

The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rdcentury CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation between diabetes and other diseases, and he discussed differential diagnosis from the snakebite, which also provokes excessive thirst. His work remained unknown in the West until 1552, when the first Latin edition was published in Venice.[130]

Two types of diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400500CE with one type being associated with youth and another type with being overweight.[128] Effective treatment was not developed until the early part of the 20th century when Canadians Frederick Banting and Charles Herbert Best isolated and purified insulin in 1921 and 1922.[128] This was followed by the development of the long-acting insulin NPH in the 1940s.[128]

The word diabetes ( or ) comes from Latin diabts, which in turn comes from Ancient Greek (diabts), which literally means "a passer through; a siphon".[131] Ancient Greek physician Aretaeus of Cappadocia (fl. 1stcentury CE) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease.[132][133] Ultimately, the word comes from Greek (diabainein), meaning "to pass through,"[131] which is composed of - (dia-), meaning "through" and (bainein), meaning "to go".[132] The word "diabetes" is first recorded in English, in the form diabete, in a medical text written around 1425.

The word mellitus ( or ) comes from the classical Latin word melltus, meaning "mellite"[134] (i.e. sweetened with honey;[134] honey-sweet[135]). The Latin word comes from mell-, which comes from mel, meaning "honey";[134][135] sweetness;[135] pleasant thing,[135] and the suffix -tus,[134] whose meaning is the same as that of the English suffix "-ite".[136] It was Thomas Willis who in 1675 added "mellitus" to the word "diabetes" as a designation for the disease, when he noticed the urine of a person with diabetes had a sweet taste (glycosuria). This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians.

The 1989 "St. Vincent Declaration"[137][138] was the result of international efforts to improve the care accorded to those with diabetes. Doing so is important not only in terms of quality of life and life expectancy but also economically expenses due to diabetes have been shown to be a major drain on health and productivity-related resources for healthcare systems and governments.

Several countries established more and less successful national diabetes programmes to improve treatment of the disease.[139]

People with diabetes who have neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be unemployed as those without the symptoms.[140]

In 2010, diabetes-related emergency room (ER) visit rates in the United States were higher among people from the lowest income communities (526 per 10,000 population) than from the highest income communities (236 per 10,000 population). Approximately 9.4% of diabetes-related ER visits were for the uninsured.[141]

The term "type1 diabetes" has replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus (IDDM). Likewise, the term "type2 diabetes" has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and noninsulin-dependent diabetes mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard nomenclature.[142]

Diabetes mellitus is also occasionally known as "sugar diabetes" to differentiate it from diabetes insipidus.[143]

In animals, diabetes is most commonly encountered in dogs and cats. Middle-aged animals are most commonly affected. Female dogs are twice as likely to be affected as males, while according to some sources, male cats are more prone than females. In both species, all breeds may be affected, but some small dog breeds are particularly likely to develop diabetes, such as Miniature Poodles.[144]

Feline diabetes is strikingly similar to human type 2 diabetes. The Burmese, Russian Blue, Abyssinian, and Norwegian Forest cat breeds are at higher risk than other breeds. Overweight cats are also at higher risk.[145]

The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals are more prone to infections. The long-term complications recognized in humans are much rarer in animals. The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of emergencies (e.g. ketoacidosis) are similar to those in humans.[144]

Inhalable insulin has been developed.[146] The original products were withdrawn due to side effects.[citation needed] Afrezza, under development by the pharmaceuticals company MannKind Corporation, was approved by the United States Food and Drug Administration (FDA) for general sale in June 2014.[147] An advantage to inhaled insulin is that it may be more convenient and easy to use.[148]

Transdermal insulin in the form of a cream has been developed and trials are being conducted on people with type2 diabetes.[149][150]

The Diabetes Control and Complications Trial (DCCT) was a clinical study conducted by the United States National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) that was published in the New England Journal of Medicine in 1993. Test subjects all had type 1 diabetes and were randomized to a tight glycemic arm and a control arm with the standard of care at the time; people were followed for an average of seven years, and people in the treatment had dramatically lower rates of diabetic complications. It was as a landmark study at the time, and significantly changed the management of all forms of diabetes.[100][151][152]

The United Kingdom Prospective Diabetes Study (UKPDS) was a clinical study conducted by Z that was published in The Lancet in 1998. Around 3,800 people with type 2 diabetes were followed for an average of ten years, and were treated with tight glucose control or the standard of care, and again the treatment arm had far better outcomes. This confirmed the importance of tight glucose control, as well as blood pressure control, for people with this condition.[100][153][154]

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Healthline Diabetes and Metabolism: What Are the Effects? – Healthline

June 24th, 2021 1:53 am

Your metabolism refers to all the chemical reactions in your body. These chemical reactions require energy. The amount of energy they require differs between people based on factors such as your age, body weight, and body composition.

Diabetes disrupts your bodys use of the hormone called insulin. This hormone regulates your blood sugar by shuttling glucose from your bloodstream to your tissues. If left uncontrolled, diabetes causes chronically high blood sugar levels that can damage your organs and blood vessels.

Here, well cover how diabetes affects your metabolism and examine the relationship between diabetes and obesity.

Every second, billions of chemical reactions occur in your body. These chemical reactions are collectively known as your metabolism.

Each of these reactions requires energy. Even extracting useable energy from your food requires energy.

Metabolic rate is the amount of energy your body burns in a certain amount of time, usually measured in calories. Its made up of three main components: your basal metabolic rate, energy burned during digestion, and energy burned through physical activity.

Your basal metabolic rate is the amount of energy your body burns at rest. It varies between people based on factors such as:

A 2014 study reviewed the results of studies published from 1920 to 2011 and found the average metabolic rate was 0.392 calories per pound of body weight per hour. For a 150-pound person, this equates to 1,411 calories per day.

The researchers found basal metabolic rate was higher in men than women and was lowest in overweight adults.

People with and without diabetes have almost identical metabolisms except for one key difference: People with diabetes have dysfunction of the hormone insulin.

Normally, after you consume food, carbohydrates are broken down by your saliva and digestive system. Once carbohydrates are broken down, they enter your bloodstream in the form of a sugar called glucose. Your pancreas produces insulin, which sends glucose to your cells for energy.

People with diabetes either dont respond to insulin or dont produce enough, or both. This can lead to chronically high blood sugar levels.

Type 1 diabetes is an autoimmune disease that occurs when the body attacks and destroys cells in your pancreas called beta cells, which produce insulin. Its usually diagnosed between childhood and young adulthood.

People with type 1 diabetes need to take insulin through injections or an insulin pump to lower their blood sugar.

Without insulin, blood sugar levels remain elevated and can cause damage to your body, leading to complications such as:

Type 2 diabetes makes up 90 to 95 percent of diabetes cases. It occurs when your body becomes insulin resistant.

Insulin resistance is when your cells stop responding to insulin and your blood sugar remains elevated.

To compensate for insulin resistance, your pancreas produces more insulin. This overproduction can damage the beta cells in your pancreas. Eventually, your pancreas wont be able to produce enough insulin to lower your blood sugar efficiently.

When your blood sugar levels remain elevated but arent high enough for you to be diagnosed with type 2 diabetes, your condition is known as prediabetes. More than 1 in 3 American adults have prediabetes.

Having obesity is the leading risk factor for the development of type 2 diabetes. Its thought to increase your risk by at least 6 times, regardless of genetic predisposition.

People who are overweight or with obesity are more likely to develop metabolic syndrome. Metabolic syndrome is a collection of five risk factors that increase your risk of developing stroke, type 2 diabetes, and heart disease. The risk factors are:

Researchers are still investigating why people who have obesity are more likely to develop diabetes than people who do not have obesity. One theory is that people who have obesity have increased levels of free fatty acids in their blood, which may stimulate the release of insulin and contribute to the development of insulin resistance.

People with diabetes often need to take insulin to keep blood sugar levels at a normal level. Insulin is usually taken through injections via pens or syringes. You can also take insulin through an insulin pump inserted under your skin.

Another option is inhaled insulin that you breathe in through your lungs. This type of insulin is absorbed quickly and wears off quicker as well 1.5 to 2 hours compared to 4 hours with rapid-acting injectable insulin.

There are five main types of insulin that help keep blood sugar levels stable. A doctor can help you decide which is best for you.

Taking too much insulin can lead to low blood sugar, which can be potentially life-threatening in severe cases. Going a long time between meals, skipping meals, or exercising can contribute to low blood sugar.

Monitoring your blood sugar level regularly can help you make an informed decision about food and medications. Over time, youll develop a better understanding of how your body responds to certain foods or exercise.

To make taking the right amount of insulin easier, many people count carbohydrates. Eating a high-carb meal, especially one filled with simple carbohydrates, will cause your blood sugar levels to rise more than eating a lower carbohydrate meal, and more insulin is needed to keep your blood sugar at a normal range.

Finding the right diabetes specialist gives you the best chance of keeping your diabetes under control.

A doctor likely has experience treating patients with diabetes and can walk you through your treatment. They can also refer you to a diabetes specialist. Most diabetes specialists are endocrinologists, who are doctors trained in glands and hormones.

A healthcare professional can also help you find a diabetes education program in your area to help you learn how to best manage your diabetes. Alternatively, you can visit the American Diabetes Associations website to enroll in their Living with Type 2 Diabetes Program, or to access their other resources.

You may benefit from seeing other specialists such as personal trainers or dieticians to help with weight management. The American Academy of Nutrition and Dietetics search tool allows you to search for dieticians in your area by postal code.

Diabetes care and education specialists are also a great resource to help you manage diabetes in your daily life, including nutrition, insulin injections, and learning how to use diabetes devices.

Diabetes causes dysfunction of the hormone insulin, which impairs your bodys ability to regulate blood sugar levels. People with type 1 diabetes dont produce enough or any insulin. People with type 2 diabetes dont respond efficiently to insulin, and often the beta cells stop being able to produce a sufficient amount of insulin.

If youre diagnosed with diabetes, its important to follow your doctors recommendation and take any medications prescribed to you. Consistent high blood sugar can lead to serious complications, such as nerve damage, an increased risk of infection, and cardiovascular disease.

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