MONDAY, July 18, 2022 (HealthDay News) -- For thousands of years, people have used meditation to help diminish their pain but how the process works has always seemed rather mysterious.

Today, advanced brain scan technology has revealed how this ancient practice alters brain function and provides pain relief to its practitioners.

A first-of-its-kind study used MRI scans to discover that mindfulness meditation can interrupt the communication between brain areas that process pain and the neural network that produces a person's sense of self, researchers recently reported in the journal PAIN.

Essentially, pain signals still move from the body to the brain, but the meditating person feels less ownership over those pain sensations. As a result, their pain and suffering are reduced.

"It's still going to be painful. It's just not going to bother you as much," said senior author Fadel Zeidan, an associate professor of anesthesiology at the University of California San Diego School of Medicine. "The significance of what it means for who you are as a person is being diminished. This is no longer my pain. It just is."

For the study, Zeidan and his colleagues taught meditation to 20 people through four separate 20-minute mindfulness training sessions. Another 20 people listened to a book on tape for the same amount of time, to serve as a control group.

The researchers then placed all participants in an MRI scanner with a plate on the back of their leg that produces painful sensations of heat without causing a burn. Participants received painful heat for 10 episodes -- 12 seconds on, 12 seconds off, Zeidan said.

Participants reported their levels of pain during each brain scanning session, with the people who were taught meditation using the practice to diminish their pain.

People reported a 33% decrease in pain when they used meditation, Zeidan said.

In fact, the people in the control group who didn't know how to meditate experienced a 20% increase in their pain from the beginning to the end of the MRI session, as they became more sensitive to it, Zeidan said.

These results were expected. More interesting is what the MRI scans revealed.

Researchers found that meditation was associated with reduced synchronization between the thalamus -- part of the brain that relays incoming sensory information -- and a group of brain regions known the default mode network.

The default mode network is most active when a person is mind-wandering or processing their own thoughts and feelings. One part of this network is the precuneus, a brain area involved in fundamental features of self-awareness and one of the first regions to go offline when a person loses consciousness.

"The precuneus is super cool," Zeidan said. "It consumes the highest caloric metabolic energy in the brain, and is situated in the brain to integrate all sensory systems into one cohesive stream of self-referential consciousness."

The MRI scans showed that meditation produced greater decoupling between the thalamus and the precuneus, he said.

"We think what happens is that greater pain relief is being driven by the lack of communication between the thalamus and the precuneus," Zeidan said. "The thalamus takes in all this pain-related information from the body, but it stops sending it to the precuneus. That stops the integration of this pain-related sensor information into self, into self-reference."

In other words, he said, the two regions are decoupling the appraisal of what that information means to them. "The more they're able to do that and let go, the better the pain relief," Zeidan said.

The default mode network "has been a very hot topic in neuroscience for the last 10 years, because the more you're involved this self-reference network, the less happy people are, the more depressed or anxious, and the more chronic pain they have," Zeidan said.

"This is the first study to show that this network can play a pain-modulatory role, which is pretty exciting," he said.

If this proves out, meditation could become a common practice taught by doctors or pain specialists to help people deal with problems like chronic low back pain, Zeidan said.

"If you think about it, is there anything out there that we can use to reduce someones chronic pain immediately, so they can move on with their day?" he said. "I don't know of anything, really. You can take ibuprofen or whatever, but youve got to wait 45 minutes, if that works even. Meditation can immediately produce benefits."

Dr. Houman Danesh, director of Integrative Pain Management at the Icahn School of Medicine at Mount Sinai in New York City, reviewed the findings.

This study provides "a good basis to start doing more research into" meditation for pain relief, he said.

"What they're saying with the regions of the brain that are involved and how it decouples, it makes complete sense," Danesh said.

He added that this gets into how complex pain really is.

"We often think of pain that when you touch something hot and you pull your hand back, but it's not that simple," Danesh said. "There are hundreds of thousands of inputs that go up into the brain and hundreds of thousands that come down. And then that overall process is how you experience pain."

Studies like this, which use rigorous science to better understand meditation, could help the practice become as widely accepted as acupuncture -- another ancient art for which the medical evidence has become so compelling that the Centers for Medicare and Medicaid Services now covers its use, Danesh said.

"We all agree that the mind and body are connected, and then when you start trying to delve further into it is when it starts sounding a little bit hokey and a little standoffish," Danesh said. "But in reality, the premise of the mind and body are connected is accepted by almost everybody. And so being able to tap into that can literally transform the way pain is controlled in our society."

More information

The U.S. National Institutes of Health has more about meditation and mindfulness.

SOURCES: Fadel Zeidan, PhD, associate professor, anesthesiology, University of California San Diego School of Medicine; Houman Danesh, MD, director, Integrative Pain Management, Icahn School of Medicine at Mount Sinai, New York City; PAIN, July 7, 2022

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This story is part of Health by the Numbers, CNET's deep dive into how we quantify health.

Is punching health data into your phone or constantly checking your watch to see how much oxygen your blood has starting to feel like a chore?

We live in a time where the line between our bodies and our data is getting increasingly blurry. With the availability of apps that track our menstrual cycles and watches that can tell how stressed we are, there's pressure to keep tabs on any incremental changes to our health metrics. If we don't, how can we possibly know if we're healthy?

While tracking such metrics can be helpful (or even fun), it's not necessary to live a healthy life. In fact, if you stay tuned in to your body, you'll be able to gauge your well-being through some key patterns.

Here are a few health clues.

This applies to both bowel movements and menstrual cycles (for people that have one). Just like the nonexistent hands on our smartwatches, our bodies like to keep a rhythm.

Having at least one bowel movement a day is a good sign that your digestive system is working properly, and anywhere from three a week to three a day is considered normal. (Bonus points if you normally go around the same time each day.) Painful or infrequent bowel movements could be signs of constipation or irritable bowel syndrome -- conditions that flag a reason for a doctor's visit.

Regular bowel movements may also be signs of a healthy gut microbiome, which some researchers believe we're just beginning to scratch the surface on how connected it is to our other body systems.

Another pattern: regular menstrual cycles (occurring each month between 24 and 35 days) are not only a sign of reproductive health and regular ovulation, but they're also a signal that your hormones are balanced. Hormonal imbalances can be a product of stress (which has a myriad of effects on well-being), over-exercising or illness, like thyroid disease. For people who menstruate, the monthly cycle can be one of the first things thrown off track when there's a disruption in the carefully orchestrated hormonal dance. (Note that while you're taking hormonal birth control pills or have a hormonal IUD, your body won't have a "normal" menstrual cycle and a missed or late period may not be as big of a deal.)

According to the American Academy of Sleep Medicine, adults should get at least 7 hours of sleep for optimal health. And while there's no shortage of reasons why many people are behind on their sleep, or even chronically sleep deprived, lack of sleep contributes to a variety of social and health problems, including hormonal imbalances, mood issues and even a greater risk of a heart attack.

If you're feeling sluggish, foggy or just plain tired many days, a more refreshed feeling might come after a schedule change or stress reduction. But if you're getting at least 7 hours and feel you should be a lot more energized than you really are, it could signal a more serious health problem such as sleep apnea or a nutrient deficiency like iron. If that's the case, make an appointment with a health care provider to get to the bottom of it.

Read more tips on how to get better sleep.

When you're getting enough shut-eye and wake up most days feeling refreshed, that's a good sign your body's getting the rest it needs.

A little morning or onion breath is par for the coursem and your breath might be a little off if you're dehydrated. But a weird taste or smell in your mouth during the day after you've already brushed your teeth could be a sign something is up.

"Fresh breath is a good indication that your gut health is balanced," Dr. David Borenstein of Manhattan Integrative Medicine told The Healthy.

"For example, overly fruity smelling breath can be an indication of diabetes, foul-smelling breath can be associated with reflux, a fishy smell could mean kidney failure, a sour mouth can be a sign of sleep apnea," he said.

Like our gut microbiome, there's evidence that suggests a disruption in the microbiome in our mouths can affect our health in more general ways. According to the Mayo Clinic, poor oral health (including tooth decay or gum infections) could increase your risk for developing heart problems, pregnancy complications or even pneumonia.

Urine that's pale yellow is a clear indication that you're hovering around a healthy level of hydration, according to the Cleveland Clinic. Drinking enough water is one of the easiest ways to keep your body healthy, as hydration aids important processes like regulating body temperature, preventing infections and improving cognition (hello, dehydration brain fog). So if you normally pee a lighter shade of yellow as opposed to a strong, dark color, you can find some peace that your body is getting enough water. How much you need, of course, varies by many factors including activity level.

Read more: How Much Water Do You Really Need to Drink Each Day?

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Believe it or not, eating enough fat is not only good for you but also essential for your health. And there are a growing number of dietitians and nutritionists who find more health benefits in building plates around core nutrients, rather than cutting out or singling out any foods as "bad." The more restrictive diets, or diets that require you to track the calories of each food you eat, can lead to disordered eating and yo-yo dieting with no lasting health results.

The information contained in this article is for educational and informational purposes only and is not intended as health or medical advice. Always consult a physician or other qualified health provider regarding any questions you may have about a medical condition or health objectives.

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Research News

By ELLEN GOLDBAUM

A UB scientist has launched two pilot studies that focus on how dietary interventions might affect cancer treatment. One study will determine if patients on chemotherapy do better when they eat less just prior to treatment days and if they follow a plant-based diet.

The second pilot study will assess whether low protein meals may help the immune system. This study may be the only one in the country focusing on a specific dietary intervention for patients undergoing immunotherapies for cancer.

Open to patients currently undergoing chemotherapy or immune therapies for any cancer, the studies are a first step in finding out how dietary interventions may impact how tumors respond to treatment. These dietary interventions also may reduce the side effects of chemotherapy.

The studies are currently enrolling 30 patients each. More information on the studies is atclinicaltrials.gov. Patients interested in participating can call 716-878-3317.

The double goal of our studies is to improve the efficacy of therapies and perhaps to reduce the side effects from treatment, said Roberto Pili, MD, principal investigator, associate dean for cancer research and integrative oncology and chief, Division of Hematology and Oncology in the Jacobs School of Medicine and Biomedical Sciences at UB. We want to know, can lifestyle interventions help patients on cancer treatment do better?

Pili is inaugural director of UBs new Sciences, Nutrition and Cancer (SNAC) Center, which is establishing a program for integrative oncology, where dietary interventions, exercise and mind-body medicine are integrated into cancer patient care.

A better response to cancer treatment

Pili noted that there is scientific evidence that calorie restriction while patients are undergoing chemotherapy may improve their response to treatment. One small study on women with breast cancer who underwent calorie restriction for a few days prior to chemotherapy before surgery had a higher response rate to their treatment than those who didnt undergo calorie restriction.

Calorie restriction was initially proposed to ameliorate side effects from chemotherapy, explained Pili, noting that a number of studies have shown that patients who fast the day before chemotherapy may experience less nausea and vomiting.

But an even more critical advantage was observed in a recent study showing that calorie restriction also made chemotherapy more effective, allowing patients to have an improved response to treatment.

In one case, chemo completely destroyed the cancer

In one case we followed, a woman with breast cancer who agreed to undergo calorie restriction and a plant-based diet during chemotherapy prior to surgery achieved a complete response, he said. That means once they removed the breast tissue and tested it, they could not find any evidence of cancer. With the restriction in calories, the chemotherapy was able to completely destroy the cancer.

Pili said that kind of response from conventional chemotherapy prior to surgery is achieved only in about 20-30% of breast cancer patients.

With calorie restriction and a plant-based diet, we want to see if we can increase that response rate, he said. If its a 20% response rate, can we increase it to 30-40%? Could we boost that number so that more patients achieve a complete response to treatment?

Patients enrolling in the study would limit their calories every other day, starting a few days before each chemo treatment, under the direct supervision of Colleen Barrientos, registered dietician and nutritionist and a medical student in the Jacobs School, and Kyle Pasquariello, clinical oncology research coordinator in the Department of Medicine and research coordinator with General Physician, PC.

For example, if a patient has chemotherapy on a Wednesday, then calories would be restricted on the previous Friday, Sunday and Tuesday, and also on the day of treatment, Wednesday. The patient would resume a normal diet in terms of calories after the chemo administration but would remain on the plant-based diet.

Pili noted that patients who enroll will need not only to be motivated to participate, but they will also need significant support from their families. He stressed that significant scientific evidence demonstrates that patients should see a benefit.

Normal cells are more resilient to glucose starvation, he explained, but tumor cells are more sensitive to a lack of glucose, so they will be more vulnerable to the additional insult of chemotherapy. Cancer cells do not handle stress well, so they may be more vulnerable to concomitant chemotherapy and calorie restriction.

Low-protein diet may boost immune response

The potential advantage of plant-based diets is based on what is known so far about the effects of lower animal protein consumption on the incidence of certain cancers, such as prostate cancer 1.

Based on our preclinical studies, we propose a low protein diet for a couple of immunotherapy cycles, he said. It seems that the low protein diet primes the immune system, and once primed, it is easier to maintain the immune response with drugs. The low protein diet helps wake up the bodys immune response.

Results from these preliminary studies are expected within 2 to 3 years.

These are the frontiers of integrative oncology, Pili said of the pilot studies, noting that its a frontier that requires a multidisciplinary approach.

UB has all the expertise in place to bring together people from so many different disciplines, to deliver the personalized medicine and to personalize the lifestyle changes that can make each patient diagnosed with cancer have a better outcome, he said. This is not just a promise, its becoming a reality.

We know that the body has so many resources that if we leverage them, we will be able to achieve the best results from therapy and, ultimately, defeat cancer, he said.

The study is being funded by the Jacobs School and Kaleida Health through the Great Lakes Cancer Care Collaborative.

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For those diagnosed with chronic fatigue syndrome extreme exhaustion is their daily reality.

In our busy lives theres little room for extreme exhaustion; however, for those diagnosed with chronic fatigue syndrome that is their daily reality.

[IMAGE]

Chronic fatigue syndrome, also referred to as myalgic encephalomyelitis, is a little understood and complicated illness. Its hallmark symptom is extreme and persistent exhaustion. The severity of the symptoms can vary from day-to-day, completely disrupting a persons personal and work life and putting strain on their relationships and ability to make or keep plans.

By definition, chronic fatigue syndrome symptoms must be ongoing for at least six months, says Dr. Srivani Sridhar, a family physician with UW Health Northern in Rockford, Illinois. It can last several years or a lifetime without treatment. Symptoms can also wax and wane over months and years.

[READ: Adrenal Fatigue: Is It Real?]

Chronic Fatigue Syndrome Symptoms

The most common symptoms of chronic fatigue syndrome include:

Challenges with memory, concentration and focus.

Dizziness created from the movement of lying down to either sitting or standing which improves when the person lies back down.

Enlarged and possibly tender lymph nodes in the neck or armpits.

Joint pain without swelling or redness.

Persistent or extreme fatigue that is not helped by rest or sleep and affects someones ability to carry out day-to-day activities.

Post-exertional malaise which is the worsening of symptoms following either physical or mental effort.

Unexplained muscle weakness.

According to a report from the National Academy of Medicine, formerly called Institute of Medicine, an estimated 836,000 to 2.5 million Americans suffer from chronic fatigue syndrome, and at least one-quarter of patients are bed- or house-bound at some point in their illness.

Chronic fatigue syndrome strikes people of all ages, including children, across racial, ethnic and socioeconomic groups. It is diagnosed two to four times more often in women, says Dr. Avi Nath, clinical director at the National Institutes of Healths National Institute of Neurological Disorders and Stroke in Bethesda, Maryland.

[See: Top Medications That Can Make You Tired.]

Where Does Chronic Fatigue Syndrome Come From?

Researchers have yet to definitively determine what causes chronic fatigue syndrome, but potential culprits may include:

Infections. Some people develop chronic fatigue syndrome after an illness. One in 10 people who have contracted Epstein-Barr virus, Ross River virus or Coxiella burnetii will develop symptoms that meet the criteria for chronic fatigue syndrome, according to the Centers for Disease Control and Prevention.

Genetics. Researchers have found that in some cases a person has a higher chance of contracting chronic fatigue syndrome if other family members have had it. No gene has yet been definitively proven to play a role, however.

Hormones. The hypothalamus is a center in the brain that produces hormones that maintain bodys internal balance, called homeostasis. Fluctuations in hormones can be caused by sleep disturbances, infections, toxins, physical or mental stress, poor diet and autoimmune conditions. The bodys way to protect itself is to decrease energy demands on the body, resulting in fatigue.

Immune system changes. Immune systems of those with chronic fatigue syndrome appear slightly impaired, but it hasnt been determined if that plays a role in contracting the disease.

Mitochondria. Present in almost every cell in the body, mitochondria are the power houses of the cells that generate energy. When they are working inefficiently or being overused, it can lead to fatigue.

Physical or emotional stress. Some people report that shortly before their symptoms began, they experienced significant physical or emotional stress.

[See: Possible Causes of Sleepwalking.]

Diagnosing Chronic Fatigue Syndrome

CDC research showed that less than 20% of American chronic fatigue syndrome patients have been diagnosed. Diagnosing chronic fatigue syndrome remains a challenge because the symptoms overlap with many other diseases and because its a diagnosis that comes only after other illnesses are ruled out.

Most often doctors are trying to exclude other underlying diseases such as diabetes, cancer, autoimmune disorders or other brain diseases. Testing is targeted to the symptoms that they present with. There is no standard battery of tests, Nath says.

The CDC criteria for diagnosing chronic fatigue syndrome includes severe fatigue that lasts longer than six months, as well as experiencing four out of the following symptoms:

Headaches with new patterns or severity.

Joint pain without swelling or redness.

Muscle pain.

Post-exertional malaise that lasts longer than 24 hours.

Significant impairment in short-term memory or concentration.

Sore throat.

Tender lymph nodes.

Unrefreshing sleep.

A diagnosis of chronic fatigue syndrome is one of exclusion and therefore requires a thorough medical workup by your doctor. Oftentimes, people are referred to specialist doctors to rule out other illnesses, says Dr. Houman Danesh, director of integrative pain management at the Icahn School of Medicine at Mount Sinai in New York City.

According to Danesh, the most common illnesses that chronic fatigue syndrome is mistaken for are:

POTS, or postural orthostatic tachycardia syndrome, which goes undiagnosed in a lot in these cases.

Mono.

Flu.

HIV.

Lyme disease.

Hypothyroidism.

Addisons disease.

Lymphoma.

Depression.

Fibromyalgia.

Polymyalgia rheumatica.

Sjogrens syndrome.

Sleep apnea.

Parkinsons disease.

Multiple sclerosis.

Rheumatoid arthritis.

Treatment for Chronic Fatigue Syndrome

Currently there is no cure for chronic fatigue syndrome. Current treatment focuses on symptom relief. The most troublesome or disabling symptoms are typically addressed first, Nath says.

Common ways to manage chronic fatigue syndrome is to schedule activities that take into account energy levels that can help relieve some stress that the illness puts on people.

According to the American Academy of Family Physicians, cognitive behavior therapy and exercise that gradually increases over time have been shown to moderately improve fatigue levels, help patients with their day-to-day activities and manage anxiety and post-exertional malaise.

Depending on the person, chronic fatigue syndrome can last anywhere from six months to a few years, making it important to work with a health care team to find effective ways to find symptom relief and develop strategies that improve quality of life.

Take your health in your own hands and be proactive in finding an integrative or functional medicine provider that can guide you through a multi-pronged approach to support your body while it recovers and heals, eventually eliminating your symptoms, Sridhar says.

Preparing for Your Doctor Visit

Before seeing a doctor prepare a brief history that summarizes your health. Try to include:

A list of your symptoms starting with the ones that are most impactful to you.

When your symptoms started and if they began shortly after an illness or impactful event.

What makes your symptoms worse.

How the symptoms affect your day-to-day activities.

The frequency of symptoms.

In helping your doctor to make an accurate diagnosis make sure you rule out POTS by taking your pulse and blood pressure laying down, sitting and standing. Wait two minutes after changing positions. Take these recordings to your doctor who may order further tests, Danesh says. Your doctor also may repeat the tests in office.

More from U.S. News

Top Medications That Can Make You Tired

11 Signs of Postpartum Depression

7 Signs Youre Not Getting Enough Vitamin B12

Chronic Fatigue Syndrome: Symptoms and Treatments originally appeared on usnews.com

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Chronic fatigue syndrome: Symptoms and treatments - WTOP

A third of Americans believe it is harder to find a mental health care than it is to find a physical health care.

Discovery President & CEO John Peloquin states, "We are pleased to welcome the team at Anew into the Discovery family. This addition builds on our strategic mission to create a fully integrative care model, with multiple treatment models, both conventional and innovative, available through one access point. A 2022 Harris Poll report revealed that a third of Americans believe it is harder to find a mental health care provider than it is to find a physical health care provider[i]. We are removing those barriers by expanding outpatient and telehealth services in psychiatry and addiction medicine which includes TMS treatment. When people can access a wide range of behavioral health services based on their needs and preferences, they have a greater chance to live happier, more rewarding lives, and that's why we're here."

About Discovery Behavioral Health

Everyone deserves a happy, rewarding life. That's why Discovery Behavioral Health has made evidence-based, outcome driven healthcare accessible and affordable since inception. With a full continuum of care detoxification, medical residences, residential treatment centers, partial hospitalization, intensive outpatient, outpatient, psychiatric and addiction medicine, TMS, virtual and telehealth services, we can offer the right care at the right time for adults or teens struggling with mental health, substance use or eating disorders. We are a contracted provider with 100 payers and other managed care organizations. Our portfolio of more than 145 treatment centers includes service lines in successful operation since 1985. When treatment is complete, our patients become part of Discovery's growing family of alumni, connected through free aftercare programs, support groups, activities, and a caring community. Because when quality behavioral healthcare is within reach, so is happiness.

Press Contact:Greg PtacekCommunicationsDiscovery Behavioral Health, Inc.[emailprotected]323-841-8002 mobile

SOURCE Discovery Behavioral Health

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Parker Seminars Hosts NeuroCon 2022

NeuroCon Keynote Speakers

Dallas, Texas, July 18, 2022 (GLOBE NEWSWIRE) -- From July 29-30, 2022, join Parker Seminars for an exciting in-person, two-day event designed specifically for healthcare professionals! Attendees will learn from and network with well-known worldwide leaders who specialize in disorders of the nervous system. Sessions are centered around a superior integrative approach to supporting research and application for treating neurological disorders.

Taking place on the Parker University campus in Dallas, Texas, attendees will hear from industry experts and speakers, earn CE hours, and network with each other and exhibitors.

Parker Seminars is excited to announce that its keynote speakers include Max Lugavere (New York TimesBest-Selling Author and host of the No.1 iTunes Health Podcast, The Genius Life),Kimberly Noble (Professor of Neuroscience and Education at Teachers College Columbia University),Tali Sharot (Neuroscientist and Professor of Cognitive Neuroscience at University College London and MIT), andOctavio Choi (Board-certified Forensic Neuropsychiatrist and Clinical Associate Professor in the Psychiatry Department at Stanford University School of Medicine).

NeuroCon 2022 will provide attendees with the expertise needed to equip themselves and their patients with the most relevant knowledge for maximizing the brains potential. To learn more or sign up, visitneurocon.parkerseminars.com.

About Parker University

Parker University, the fourth-fastest growing college in Texas and the fastest-growing college in Dallas, was founded in 1982 by Dr. James William Parker (formerly Parker College of Chiropractic). Today, Parker University has more than 1,800 students and more than 35 academic programs,including its famed chiropractic program, as well as masters degrees in neuroscience, clinical neuroscience, strength and human performance, and functional nutrition. Currently, Parker Universitys chiropractic cohort is the second largest of any campus in the world.Parker University has been recognized as a Great College to Work For, one of the 25 Fastest-Growing Colleges in the U.S.,and as a recipient of the 2021 FutureEdge 50 Awards.

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Introduction

Galactose--1,3-galactose (-Gal), an oligosaccharide that structurally resembles blood group B antigen, is present in both glycoproteins and glycolipids from non-catarrhine mammalian muscle cells and secretions.1,2 Old World monkeys, apes and humans evolved with the inability to synthesize -Gal epitopes and, therefore, produce natural anti--Gal antibodies to control pathogen infection.3 This carbohydrate epitope is the causal agent of the -Gal syndrome (AGS), a pathognomonic immunoglobulin E (IgE)-mediated delayed anaphylaxis in mammalian meat (eg pork, beef or lamb) or dairy products 3 to 6 hours post-consumption.47 Recently, an allergic cross reaction to flounder roe in patients suffering from AGS has been reported.8 The other clinical presentations of AGS comprise immediate hypersensitivity to -Gal-containing drugs, firstly discovered using the monoclonal antibody cetuximab in anticancer therapy.6,9 There is growing evidence of allergic reactions caused by the -Gal present in mammalian substances such as gelatin, glycerin, lactic acid and magnesium stearate used in the preparation process of several medications,9,10 such as gelatin-containing products (vaccines and volume colloids), mammalian serum-based antivenom and even various analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs).2,6,11,12 The IgE initial sensitization is caused by hard-bodied tick bites from different species according to geographic location and is attributed to -Gal-containing tick salivary glycoproteins, but also other tick salivary biomolecules without -Gal modifications such as prostaglandin E2 (PGE2).1317 The mechanisms behind tick -Gal induction of sensitization are still unknown, but besides the -Gal moiety, tick sialome components may play an important role in the chained immune reaction activation (Figure 1).18,19 Tick species such as Ixodes ricinus in Europe, Amblyomma americanum in North America, Haemaphysalis longicornis in Asia and Ixodes holocyclus in Australia are linked to AGS,20 currently considered an emergent life-threatening allergy in tick endemic areas worldwide.2123 However, not all individuals bitten by ticks or those that carry elevated specific IgE (sIgE) against -Gal develop AGS, in fact, the majority only produce sIgE against it.19 Symptomatic individuals typically show delayed pruritus, urticaria (acute or recurrent), angioedema, anaphylaxis, malaise or gut-related symptoms such as abdominal pain, vomits and diarrhea.22,24,25 Anaphylaxis has been triggered in up to 60% of AGS cases and can be fatal if it is not treated promptly.2628 Clinical features reported tend to be restricted to gastrointestinal complaints, hampering the suspicion of an allergic etiology.29 Nevertheless, clinical observations in AGS patients are widely variable, showing proof of individual sensitivity.5 Augmenting factors, also called cofactors, such as exercise and alcohol intake, have been reported to play an important role in modulation of this individual susceptibility between patients.30 The medical history is of importance in these cases and details like meat-associated delayed allergic reactions and tick bite-exposure represent crucial factors for uncovering AGS, which otherwise can be misdiagnosed as idiopathic anaphylaxis or chronic spontaneous angioedema.7,30,31 Risk factors for developing sIgE to -Gal are related to the probability of individual tick bite-exposure in certain environmental conditions, including practice of outdoor activities (eg, hunting or hiking), living in rural areas, pet-ownership, and certain jobs such as forest service employees.3235 The sIgE values tend to increase according to the number of tick bites per year and on how recent those bites are.34,36 Moreover, individuals that do not have type B or AB blood group may have a higher risk of developing AGS, as blood group B antigen, similar to -Gal, creates tolerance to this epitope.37

Figure 1 Alpha-Gal syndrome (AGS). (A) Sensitization after several tick bites. Tick saliva contains glycoproteins, glycolipids with -Gal epitopes and other unknown salivary biomolecules that could be involved in the pathology of AGS. The glycan -Gal is presented to T helper 2 (Th2) cells through antigen-presenting cells (APCs) as dendritic cells, macrophages or even B cells. Once T cells are activated, B cells are leading to produce IgE against -Gal (anti -Gal-IgE) in an enriched interleukin environment and potentiate IgE production in plasma cells. Free IgE are now available to interact and bind to IgE receptors present in basophils and mast cells. (B) Allergic Reaction. When AGS patients ingest mammalian meat containing -Gal bound to proteins or lipids, these molecules expressing the allergen epitope are absorbed and incorporated to lipid/protein macromolecules during digestion (chylomicrons, lipoproteins), which will be processed and transport through protein or lipid metabolism to systemic circulation and peripheral tissues. About 36 hours post-consumption, IgE-mediated and coated effectors will recognize the allergen, leading to degranulation of basophils and mast cells and promoting a systemic delayed allergic reaction. AGS can also comprise an immediate anaphylactic reaction, triggered using -Gal containing drugs, administered via parenteral due to therapeutic reasons.

On the other hand, immune response to -Gal has been studied for the control and prevention of diseases, exhibiting a protective role in human evolution catastrophic selection. The incidence of several infectious diseases caused by -Gal containing-pathogens such as malaria or tuberculosis might be positively correlated with the frequency of the specific blood type B, and then, with a reduced immune response to -Gal. However, this fact has been associated with a lower prevalence of food allergies related to anti--Gal IgE antibodies.38 In addition, it has been recently reported a positive correlation between anti--Gal IgM antibodies and the incidence of Plasmodium falciparum infection, decreasing its transmission.39 Despite the fact that uncontrolled levels of anti--Gal antibodies could compromise health in AGS patients, these findings suggest that anti--Gal antibodies (IgE or IgM) might protect against parasites containing -Gal on their surface. Interestingly, anti--Gal antibodies have also been studied not only in vector-borne diseases but also in emerging virus infections. Recently, it has been reported that anti--Gal antibody levels negatively correlate not only with SARS-CoV-2 infection but also with COVID-19 symptomatology severity.40

Over 10 years have passed since the discovery of AGS,41 but many questions remain unclear that still need to be elucidated, especially those related to the diagnostic and therapeutical approaches used for this syndrome. The aim of the present review article is to outline current diagnostic methods used for AGS and potentially future diagnostic tools, combined with the most recent forms of treatment/management of this syndrome. Furthermore, innovative topics such as current research methods and future treatment and preventive strategies are also discussed.

The AGS is an allergic disorder that challenges clinical diagnosis due to inapparent presentation and delayed reactions.19,42 Like any other allergic disease, diagnosis relies on a well-detailed medical history in order to reach an accurate evaluation and prognostic of individual signs and symptoms.25 Diagnostic techniques for this syndrome are not specific and/or represent a risk for the patients health, whereas more precise methods still show limitations to its use.43 As discussed here, it is important to address the diagnostic tests more commonly used and methods that could potentially be employed in the future (Figure 2) for the challenging and complex allergy that involves the pathology of AGS.

Figure 2 Conventional and next generation methods for the diagnosis of the alpha-Gal syndrome (AGS).

SPTs remains a useful diagnostic tool for several food allergies.44 Conversely, conducting this test for AGS diagnosis using conventional and commercially available mammalian meat extracts (beef, pork or lamb) lacks sensitivity, yielding low-reactive results (24 mm wheals), which may lead to misdiagnosis and incorrect patient management.45 Alternatively, cancer drug cetuximab can potentially be used as a sensitivity agent due to its high capacity to induce a strong skin reactivity in AGS patients, mainly caused by the larger amount of -Gal epitopes exposed to the surface.46,47 Robust reactions also occur when mammalian meat extract is used, although this is not a feasible option for daily practice.16 Meat-derived gelatin from porcine or bovine, sometimes forming colloids, has also been used in allergic reaction diagnostics. Furthermore, it is important to consider that, although rare, the use of high-sensitivity components in SPT could potentially trigger a fatal anaphylactic shock reaction.48,49 Less commonly, intradermal testing (IDT) can also be used as a standardized methodology to evaluate skin reactions. As described by the SPT method, 20 minutes after allergen intradermal injection (around 0.1 mg/mL), swelling, redness and wheals are observed in the area of injection.50 Nevertheless, IDT is more likely to induce systemic anaphylactic reactions when compared to SPT.44 Overall, the clinical utility of SPT remains doubtful as no food allergen fits flawlessly in this diagnostic technique, conveying on several limitations and therefore making it not fit for a primary approach diagnostic tool.

For the diagnosis of a food allergy (FA), OFC is the gold standard technique, offering further information regarding food tolerability and threshold of responsiveness.51 This method could be useful for discriminating AGS diagnosis from -Gal sensitization if it did not convey to a risk of fatal or near-fatal delayed anaphylactic reactions.7,52 Therefore, this challenge can only be performed in specialized allergic centers, requiring long patient observation periods.7,53 Besides risk, OFC is not established as a standardized procedure for AGS and exposure reaction presents a high variability between patients. In fact, some patients may require the presence of cofactors in order to react, while others only respond to a particular type of red meat.54 Nevertheless, this method, tested also in combination with cofactors, is essential in patients in which drugs-containing -Gal must be given for therapeutical reasons due to the clinically relevant information that it provides.55 Cofactors, such as acetylsalicylic acid (ASA) or alcohol, are well-known amplifiers of -Gal reactions.6 Due to the wide difference between symptomatology of AGS patients, sensitivity to -Gal can be truly variable.30 However, it has been observed that pork kidney intake, and no other product like muscle meat, even in the coadministration of cofactors, is a key element to raise AGS symptoms. This difference might be explained due to the higher number of -Gal epitopes present in pork or beef kidney in comparison to other meats/innards.56,57

Currently, serum anti-Gal IgE levels measured using an immune-enzymatic assay (bovine thyroglobulin-conjugated ImmunoCAP) is the confirmatory diagnostic method used for AGS diagnosis when medical history matches with this disease.5860 Nonetheless, it remains unclear the clinical relevance of positive testing for anti-Gal IgE using a cut-off value of 0.35 kU/L (where 1 kU/L = 1 IU/mL = 2.4 ng/mL).33,42,46,52,61 While Mabelane et al54 state that 5.5 kU/L is the cut-off point for clinically significant AGS, other studies reveal that there are no strict criteria regarding anti-Gal IgE levels as an allergic symptomatology predictor.25,62 One thing is clear, though, is that levels of specific IgE are not a useful biomarker for predicting the severity of allergic reactions, as AGS patients experiencing anaphylactic reactions may maintain IgE levels overtime or even in rare occasions with anti-Gal IgE negative results.25,63 Another issue with the anti-Gal IgE diagnostic assay is that it can lead to false-positive results in those individuals where Gal IgE sensitization may also be related to bee and wasp stings, parasitism, atopy or cat ownership, creating cases where these antibodies do not match the clinically pathognomonic history of AGS.25,42,62,64,65 For example, in a clinical study carried out in southern Germany, among 300 hunters with a 19.3% of IgE--Gal prevalence (58 individuals positive for cut-off value of 0.35 IU/mL), only 1.67% (5 individuals of the initial cohort) had allergic reactions to mammalian meat.33 Moreover, serum levels of IgE to Gal tend to drop when patients do not experience recurrent tick bites, but again, the rate of declination between individuals is widely variable, being therefore recommended to repeat testing every 8 to 12 months.25,45 Nevertheless, due to AGS non-related therapeutical reasons, sometimes the measurement of anti-Gal IgE levels may be needed to detect Gal sensitization and therefore prevent drug-induced anaphylaxis.60 In summary, anti-Gal IgE levels may be useful for AGS diagnosis, but clinical symptomatology and disease severity cannot be evaluated exclusively through this parameter, requiring complementation with other diagnostic techniques.

Over the years, research studies allowed to recognize distinct improved biomarkers that provide a more accurate diagnosis of food allergies.66 This led the way to the use of the in vitro functional assay BAT, a flow-cytometry-based technique that quantifies the expression of activation membrane markers, namely, CD63 and CD203c, in order to analyze basophil degranulation when triggered by a specific allergen.6668 In the research setting and specialized referral centers, BAT is being used as a diagnostic clarifier, allowing to distinguish between merely asymptomatic sensitized individuals and patients suffering from AGS.42,53,69 This newly emerging method offers good sensitivity and specificity, but presents several practical and logistical issues for implementation in clinical practice.43,70 First, blood must be processed within 24 hours after being collected in order to guarantee that basophil viability and reactivity are preserved.6,71 Second, questions regarding reproducibility and cost must be addressed before BAT implementation in practicing allergists.72 Unfortunately, methodology, concentration and markers are not standardized between laboratories in order to allow result comparison and test validation.73 Furthermore, standardization between systems and instruments required for accreditation (eg, EuroFlow Standard Operating Procedures) is missing, reducing BAT availability.74,75 This technique also lacks an established proficiency testing by regulatory entities. The current European Directive 98/79/EC on in vitro diagnostic medical devices76 will be replaced in 2022 by the new Regulation (EU) 2017/746 and introduce major changes in the sector, aiming for a smooth functioning of the internal market.77 In sum, efforts should be made to convey on transforming BAT into an on-hand tool for clinicians, due to the benefits it presents on risk allergy stratification, precise decision-making for -Gal sensitized patients who lack medical evidence and selection of the correct doses for OFC in AGS-suffering individuals.53,72

Another in vitro assay executed by flow cytometry is the MAT, a technique that measures CD63, a membrane activation marker that increases when mast cells (MCs) degranulate. This phenomenon occurs when MCs are triggered by allergen-sIgE antibodies.66,78 MAT presents high sensitivity and leads to a dose-dependent response to allergens,79 making it a potential and attractive complementary candidate for AGS diagnosis. Furthermore, MAT seems to overcome BATs major limitations. First, the use of MCs rather than basophils appears to be more suitable for allergy diagnosis due to the well-recognized effector function of MCs in comparison to the mere regulatory activity of basophils.80 Secondly, serum samples can be frozen prior to their use, as MAT does not require fresh viable cells, facilitating logistics and sample shipment if required.81 The MCs line can be activated directly through mas-related G protein-coupled receptor X2 (MGPRX2) with simultaneous analysis of positive and negative populations for this receptor. Herein, MC degranulation can be studied via upregulation of specific degranulation markers, such as CD63. Most common MRGPRX2-expressing cell lines used in combination with CD63 detection by flow cytometry are LAD-2 cells derived from human CD34+ cells.82,83 However, there is still a long way to go from standardization to validation to obtain a fully functional MAT assay, as currently this technique is particularly time-consuming and several key issues still persist regarding heterogeneity of MCs.70,84 Although MAT test is still under validation for clinical application, it represents a promising diagnostic approach, particularly as a confirmatory test when conventional methods generate ambiguous results.66,82

Another emerging diagnostic test in the FA field is the HR assay, a standardized test based on fluorescence intensity that measures the amount of histamine released by activated basophils.85 Although even further studies are required to support standard results, this technique could potentially be used for AGS diagnosis since basophil reactivity was found to be higher in these patients when compared to -Gal sensitized individuals.10 Indeed, this method displays similar high sensitivity and specificity values when compared to the BAT test,86 but further studies are required to support this result, especially involving AGS-suffering patients.

Collective characterization and quantitation of biomolecules known as omics technologies such as metabolomics, metagenomics, proteomics and transcriptomics could advance knowledge of the immune response in AGS and its molecular drivers, enabling the identification of biotargets for molecular diagnosis of this global impact disease.10,87 Not only the identification of host biomarkers and host-derived immune response mechanisms but also tick-derived biomolecules are important for the development of new diagnostic tools.52 Proteins present in tick sialome, especially highly conserved across tick species, could potentially serve as diagnostic antigens.47 A recent study by Villar et al88 identified by proteomics analysis of tick sialome and alphagalactome the 14-3-3 family chaperone that could possibly constitute a future diagnostic disease biomarker. The study identified that 14-3-3 family chaperone and other proteins were recognized by IgE in sera from AGS patients.88 Therefore, they proposed that these proteins may potentially be involved in the AGS and other disorders with the possibility of mediating protective immune mechanisms against tick infestations and pathogen infection.88 Nevertheless, there are also tick salivary gland proteins with non--Gal modifications that could probably be used to develop ELISA tests for antibody quantification as a complementary diagnostic method for AGS.47,52,89

Artificial intelligence (AI) and machine learning are considered to be powerful diagnostic assistance tools, which in the future could revolutionize the healthcare system providing an accurate and custom-based diagnosis.90 MBR algorithms aim to create a clinical diagnosis or decision-making model that utilize hybrid reasoning and data-driven AI in order to obtain high diagnostic yields by combining the integrative medicine concept.91 For puzzling and complex diseases, such as AGS, in which diagnostic tools lacking standardization and cofactors are also involved, the use of this integrative diagnostic technique could represent the best fitting method. The use of this methodology has been proposed by de la Fuente et al52 for improving AGS diagnosis, considering together clinical symptoms, risk factors and anti--Gal sIgE levels. They also proposed that the machine learning algorithm could be transformed into a code for a software creation with further implementation in clinical practice via mobile applications.52

Ticks are today the most accepted evidence for sensitization to -Gal, but other risk factors or co-factors are likely relevant.92 Daily diet counseling, tick bite avoidance or environmental education should be firstly considered in customizing an accurate treatment for the AGS.42,61 Subsequently, an expertise behind medical interventions is required for an adequate management of the disease over time.43 Although most cases are not emergency cases, invasive techniques are required for in shock patients treatment.6 Furthermore, established protocols, symptomatology, or information about the AGS characteristics are not available due to the wide natural history and variety of subjects all over the world. Herein we present some of the most common strategies and routinary methodology in AGS treatment/management when the disease is diagnosed.

The pillar of the non-medical approach is based on avoidance. The prevention of tick bites is relevant because continuous exposure to tick bites may maintain or increase anti--Gal IgE titers and lead to allergic responses to previously tolerated foods.92 Despite limited evidence, patients who successfully avoid tick bites on a long term (12 years) have a higher chance of recovering tolerance to meat products, allowing the reintroduction of red meat into diet.10,42,93 The most common strategy for tick-bite prevention and management includes the use of lighter colored protective clothes treated with insect repellents or insecticides such as permethrin.21 Furthermore, prompt embedded tick removal using specialized fine-tipped forceps should be performed in order to reduce the amount of secreted salivary allergens.24,92

Secondly, avoidance of mammalian meat, by-products of meat (innards), fat (gelatin and lards) and other -Gal-containing foods such as dairy products represent a crucial management strategy for AGS.10,92 To achieve this goal, dietary counseling is vital, and it can be combined with nutro clinical support to avoid nutritional deficiency, especially in highly sensitized individuals.6 Patients should receive a personalized dietary follow-up depending on which foods are allergy triggering and to routinely check for iron and vitamin B12 supplementation needs.21,61

Another major foundation for AGS management is education. Vulnerable patients should be taught on nutrition facts label reading, awareness of hidden exposures and be provided with a written plan on how to promptly operate in case of an allergic reaction.6,42,61 Clinicians must also inform patients of the risk of onset anaphylaxis not only due to cetuximab but also because of heparin, gelatin-containing vaccines and mammalian heart valves.94 The fact that numerous pharmaceutical products contain animal-derived excipients makes it harder to avoid all potentially immunogenic antigens.95 For this reason, it is recommended for AGS-suffering patients to wear warning bracelets about their condition so that physicians are aware and can prevent future life-threatening situations in emergency cases.61 In fact, due to the worldwide increase in individuals with high anti--Gal IgE titers and possibly undiagnosed AGS-patients, an allergy prescreening before administration of -Gal containing medication might be recommended.96

Due to the AGS delay and unexpected symptomatology, emergency treatment is of utmost importance to correctly manage allergic reactions and potentially life-threatening anaphylaxis.6 Furthermore, the high variability regarding severity and timing of the symptoms represents a challenge for the medical management of this disease.21 Intramuscular epinephrine administration represents the initial recommendation. For patients in shock, intravenous epinephrine should be applied alongside with fluid resuscitation and occasional vasopressors. In case of airway obstruction, intubation may be necessary.97 Afterwards, in order to properly reduce the risk of a multisystem allergic reaction, it is imperative to always carry an epinephrine auto-injector.21 For tick-bite local reactions, symptomatic treatment with oral antihistamines, corticosteroids and cold compresses should be enough to reduce non-serious symptoms such as pruritus, urticaria and angioedema.98 As AGS symptomatology and severity are reported to have high individual variability and rely mostly on symptomatic treatment, information collected mostly from case reports is presented in Table 1, together with their clinical management apart from the anaphylaxis acute treatment-response already discussed. A recent study described a clinical case with abnormal neuro-psychiatric behavior (abulia, aphasia, abnormal gait, and reduction of limb movement) related to AGS and a possible -Gal driven immune-related hypothalamic dysfunction that needs further investigation.99 Other symptomatology such as palpitations and tachycardia are self-limiting and therefore resolve spontaneously.100

Table 1 Drugs and Associated Pharmacological Class Used for -Gal Syndrome Medical Treatment

As described above, humans evolved as non-capable organisms to produce the glycan -Gal.114 Together with the fact that a wide variability exists between individuals suffering from this disease,5 AGS comprehension becomes a complex goal in which molecular and physiological mechanisms need to be elucidated. Several experimental model hosts are currently available for the study of AGS and the immune response to -Gal. Zebrafish (Danio rerio) model has been established and validated under laboratory conditions. This animal model was developed by Contreras et al,115 in which allergic hemorrhagic anaphylactic-type reactions together with behavior changes and mortality were observed in response to tick salivary compounds and mammalian meat consumption. The reactions were associated with tissue-specific toll-like-receptor-mediated responses in Th1 and Th2 helper cells. These data support the use of zebrafish as an animal model for the study of the AGS and bring a new perspective for future strategies in the control of infectious diseases as reported for tuberculosis using vaccination with -Gal.116

Murine models have been used for decades as validated experimental in vivo methodology for investigating both human and animal diseases due to the advantages that these models offer in terms of time, reproducibility and genetic characteristics.117,118 However, wild-type mice produce biologically active 1,3-galactosyltransferase (1,3GT) for the synthesis of -Gal and thus lack anti-Gal antibodies.119 Knocking out the 1,3GT gene results in the absence of -Gal epitopes, not only in murine models but also in pigs,120,121 thus becoming humanized experimental animal models.

The mice C57BL/6 line is one of the most common strains used in research.122 The humanized murine model of this strain for studying AGS (GTKO, AGKO or 1,3-GalT-KO), has been used for the study of tick-induced IgE response-model for -Gal reactions,123,124 but also for testing other immunological approaches as tick-borne allergies and Chagas disease investigation.125,126

Using these animal models, further research is needed to investigate AGS risk factors and epidemiology in order to propose an accurate treatment strategy for each patient.

Mammalian meat desensitization by oral immunotherapy (OIT) has been proposed as a promising treatment for AGS as it would improve patients welfare and safer management.127 It consists of daily intake of small and generally increasing amounts of allergen, in order to reduce the immune response and consequently produce own allergen desensitization.128 To date, there are only three successful case reports (two adults and one pediatric case) of AGS with oral desensitization to beef meat.127,129 Although this type of treatment leads to a sustained unresponsiveness,93 it requires an individual effort from the patient to consume daily 120 grams of cooked mammalian meat in order to maintain desensitization,129 which also becomes an obligation and can have an impact on the patients routine, commodity and mental wellbeing. Indeed, daily mammalian meat intake could compromise the patients to develop other metabolic and cardiometabolic diseases such as hypertension, diabetes and obesity.130,131 Additionally, allergen-specific immunotherapy (AIT) using natural and recombinant -Gal containing proteins from tick sialome is also being considered for AGS treatment.17 Nonetheless, this type of therapies comes with a risk of life-threatening anaphylactic adverse reactions and demand a thoughtful and balanced management of accurate dose efficacy versus side effect appearance.66,132

Given the potential risks associated with immunotherapy, the use of allergen non-specific treatments, such as anti-IgE therapeutic monoclonal antibodies (mAbs), has found application in the treatment of food allergy.133,134 In anti-IgE therapy, mAbs bind to free serum IgE and IgE-coated B cells, acting as a competitive substrate and reducing the availability and binding between these antibodies (natural IgE) and allergy mediators such as basophils and mast cells, which increases reaction threshold and consequently reduces the risk of mild and severe anaphylactic reactions (Figure 3).43,134 Combining anti-IgE therapy as a pre-treatment with immunotherapy techniques leads to a safer administration of OIT and allows to reach the maintenance dose more rapidly.128,133,135 The anti-IgE agent omalizumab has been sporadically used in specialized centers as monotherapy in AGS patients for successfully controlling continued reactivity, allowing the introduction of a small amount of mammalian meat in their diet.42 With such a positive preliminary outcome in these patients and promising data results in other FAs (peanut and cow milk), new clinical trials using biological therapies for AGS are needed, potentially representing a future effective treatment.42,43,133

Figure 3 Anti-IgE therapy. IgE-mediated reaction with release of histamine and other co-factors occurs due to interaction of allergen-specific IgE available with IgE receptor in mediator cells (basophils, eosinophils or mast cells), which are degranulated and increase the risk of life-threatening anaphylactic adverse reactions. The pharmacological and clinical aims of the use of anti-IgEs monoclonal antibodies (mAbs) as drugs is to downregulate and/or decrease IgE production by B cells. Anti-IgE antibodies bind to both IgE-expressing B cells and free serum IgE, markedly decreasing IgE levels available for binding to IgE receptor in allergic reaction-mediator cells and, consequently, gradually compromising mast cells and basophils sensitivity to allergens.

Management of FAs is becoming less generic and more target oriented.66 Consequently, there is still a need to improve our understanding of the immunological mechanisms behind tick bite sensitization and therefore identify new and more specific targets for the development of new treatment interventions for AGS.136

Prevention from developing AGS stands on avoiding the initial -Gal sensitization caused by tick bites, being particularly beneficial for at-risk population.21,35,36 Apart from the common strategies for tick-bite prevention mentioned above, the development of tick-antigen-based vaccines could not only protect against AGS but also against other tick-borne diseases.14

Therefore, to follow the vaccinomics approach, it is essential to identify tick bioactive molecules and consequent signaling pathways that mediate tick-host-pathogen interactions.137,138 For example, in a study by Mateos-Hernndez et al,47 tick sialome proteins, with or without -Gal modifications, that led to a protective immune response and were recognized by AGS patients but not control individuals could serve as potential target antigen candidates for vaccine development. The identification of the poorly understood molecular mechanisms behind the development of spontaneous acquired tick resistance (ATR) is also of key importance as it could help in the search for new vaccine formulations.139 Discovering which tick salivary antigens are natural targets of ATR will help to aim towards the inhibition of tick feeding, reproduction and further pathogen transmission.140

AGS is an atypical, underdiagnosed vector-borne allergy that presents clinical implications beyond expected due to the presence of -Gal in various animal-derived medical products, hindering the treatment of several other pathologies.141 Since the discovery of AGS, many advancements have been made in order to obtain a better knowledge in terms of disease epidemiology, medical approach and molecular mechanisms. Nevertheless, current diagnostic methods lack specificity or are too risky for routinary appliance, creating the need to overcome these limitations with more precise methods. Also, a uniformization-based approach of diagnostic guidelines could be beneficial, creating comparable data and offering an opportunity to improve clinical decision-making accuracy. Further diagnostic, treatment and preventive advances will only be possible if the molecular and immune mechanisms behind AGS are uncovered. Furthermore, it is of utmost importance to identify tick salivary molecules, with or without -Gal modifications, that trigger IgE sensitivity as they could be the key for further vaccine development. With climate change, the tick-host paradigm will shift towards an increasing number of AGS cases in new regions worldwide,22 which will pose new challenges for clinicians in the future.

Research on AGS was funded by Ministerio de Ciencia e Innovacin/Agencia Estatal de Investigacin MCIN/AEI/10.13039/501100011033, Spain and EU-FEDER (Grant BIOGAL PID2020-116761GB-I00). R. Vaz-Rodrigues was supported by a doctoral contract (2022/20675) from Universidad de Castilla-La Mancha (UCLM), Spain, co-financed by the European Social Fund (ESF). L. Mazuecos was supported by a post-doctoral grant (2021-POST-32002) from UCLM co-financed by ESF.

The authors declare that they have no conflicts of interest in this work.

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Diagnosis and treatment of the alpha-Gal syndrome | JAA - Dove Medical Press

Bastyr University is proud to announce its first fully online degree program, the Master of Science in Integrative Nutrition.

KENMORE, Wash., July 14, 2022 /PRNewswire-PRWeb/ -- Bastyr University announces the launch of its Master of Science in Integrative Nutrition (MSIN), available online starting Fall 2022. The MSIN is an accelerated, two-year program that prepares its graduates to be integrative nutrition experts. The program allows students in the program to take one course at a time, making it ideal for adults working full-time.

Bastyr created the online MSIN program in response to demand from prospective students outside of the geographic radii of its Seattle and San Diego area campuses, as well as to address the need for integrative nutrition experts in our health system.

"Making innovative nutrition education accessible to more people, everywhere, is a step forward for Bastyr University and the people our graduates serve as they help others build healthier bodies, minds, and spirits," says Bastyr University President Devin Byrd, Ph.D."It's online, one course at a time format makes this ideal for working professionals everywhere."

Upon degree completion, graduates can continue their education at the doctoral level or move into the workplace in areas such as:

A key distinction of this program is its intersectionality of diet, lifestyle, environment, and culture. MSIN students learn about culinary medicine, dietary supplementation, disease prevention through nutrition, social justice and food systems, whole food nutrition, and gain research skills that foster a passion for lifelong learning.

Bastyr University is an accredited, nonprofit, private university offering doctoral,graduate,and undergraduate degrees, with a multidisciplinary curriculum in science-based natural health and medicine. Recognized globally for its rigorous curriculum and strong research, Bastyr University has campuses in Kenmore, Washington, and San Diego, California. Bastyr's facultyeducatefuture leaders in the natural health arts and sciences, with an emphasis on integrating mind, body,spirit,and nature.

For more information about the MSIN program, visit https://bastyr.edu/academics/nutrition/master-science-integrative-nutrition-online.

Media Contact

Nicole Francois, Bastyr University, 206.799.4414, nicole@marketwellnow.com

SOURCE Bastyr University

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New Online Program: Master of Science in Integrative Nutrition - Classes Begin Fall 2022 - Benzinga - Benzinga