Cold planets exist throughout our galaxy, even in the galactic bulge, research suggests

 Although thousands of planets have been discovered in the Milky Way, most reside less than a few thousand light years from Earth. Yet our Galaxy is more than 100,000 light years across, making it difficult to investigate the Galactic distribution of planets. But now, a research team has found a way to overcome this hurdle.

In a study published in The Astrophysical Journal Letters, researchers led by Osaka University and NASA have used a combination of observations and modeling to determine how the planet-hosting probability varies with the distance from the Galactic center.

The observations were based on a phenomenon called gravitational microlensing, whereby objects such as planets act as lenses, bending and magnifying the light from distant stars. This effect can be used to detect cold planets similar to Jupiter and Neptune throughout the Milky Way, from the Galactic disk to the Galactic bulge -- the central region of our Galaxy.

"Gravitational microlensing currently provides the only way to investigate the distribution of planets in the Milky Way," says Daisuke Suzuki, co-author of the study. "But until now, little is known mainly because of the difficulty in measuring the distance to planets that are more than 10,000 light years from the Sun."

To solve this problem, the researchers instead considered the distribution of a quantity that describes the relative motion of the lens and distant light source in planetary microlensing. By comparing the distribution observed in microlensing events with that predicted by a Galactic model, the research team could infer the Galactic distribution of planets.

The results show that the planetary distribution is not strongly dependent on the distance from the Galactic center. Instead, cold planets orbiting far from their stars seem to exist universally in the Milky Way. This includes the Galactic bulge, which has a very different environment to the solar neighborhood, and where the presence of planets has long been uncertain.

"Stars in the bulge region are older and are located much closer to each other than stars in the solar neighborhood," explains lead author of the study Naoki Koshimoto. "Our finding that planets reside in both these stellar environments could lead to an improved understanding of how planets form and the history of planet formation in the Milky Way."

According to the researchers, the next step should be to combine these results with measurements of microlens parallax or lens brightness -- two other important quantities associated with planetary microlensing.

Source: ScienceDaily

Gut bacteria influence brain development

 Extremely premature infants are at a high risk for brain damage. Researchers have now found possible targets for the early treatment of such damage outside the brain: Bacteria in the gut of premature infants may play a key role. The research team found that the overgrowth of the gastrointestinal tract with the bacterium Klebsiella is associated with an increased presence of certain immune cells and the development of neurological damage in premature babies.

Complex interplay: the gut-immune-brain axis

The early development of the gut, the brain and the immune system are closely interrelated. Researchers refer to this as the gut-immune-brain axis. Bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve as well as via the immune system. "We investigated the role this axis plays in the brain development of extreme preterm infants," says the first author of the study, David Seki. "The microorganisms of the gut microbiome -- which is a vital collection of hundreds of species of bacteria, fungi, viruses and other microbes -- are in equilibrium in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain," explains the microbiologist and immunologist.

Patterns in the microbiome provide clues to brain damage

"In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury," adds David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as Operational Director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna. "Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided."

Comprehensive study of the development of extremely premature infants

Starting points for the development of appropriate therapies are provided by the biomarkers that the interdisciplinary team was able to identify. "Our data show that excessive growth of the bacterium Klebsiella and the associated elevated ??-T-cell levels can apparently exacerbate brain damage," explains Lukas Wisgrill, Neonatologist from the Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics at the Department of Pediatric and Adolescent Medicine at the Medical University of Vienna. "We were able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system and the brain develop and how they interact in this process," he adds. The study monitored a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods -- the team examined the microbiome using 16S rRNA gene sequencing, among other methods -- the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants' brains.

Research continues with two studies

The study, which is an inter-university clusterproject under the joint leadership by Angelika Berger (Medical University of Vienna) and David Berry (University of Vienna), is the starting point for a research project that will investigate the microbiome and its significance for the neurological development of prematurely born children even more thoroughly. In addition, the researchers will continue to follow the children of the initial study. "How the children's motoric and cognitive skills develop only becomes apparent over several years," explains Angelika Berger. "We aim to understand how this very early development of the gut-immune-brain axis plays out in the long term. " The most important cooperation partners for the project are already on board: "The children's parents have supported us in the study with great interest and openness," says David Seki. "Ultimately, this is the only reason we were able to gain these important insights. We are very grateful for that."

Source: ScienceDaily

Engineers grow pancreatic 'organoids' that mimic the real thing

 MIT engineers, in collaboration with scientists at Cancer Research UK Manchester Institute, have developed a new way to grow tiny replicas of the pancreas, using either healthy or cancerous pancreatic cells. Their new models could help researchers develop and test potential drugs for pancreatic cancer, which is currently one of the most difficult types of cancer to treat.

Using a specialized gel that mimics the extracellular environment surrounding the pancreas, the researchers were able to grow pancreatic "organoids," allowing them to study the important interactions between pancreatic tumors and their environment. Unlike some of the gels now used to grow tissue, the new MIT gel is completely synthetic, easy to assemble and can be produced with a consistent composition every time.

"The issue of reproducibility is a major one," says Linda Griffith, the School of Engineering Professor of Teaching Innovation and a professor of biological engineering and mechanical engineering. "The research community has been looking for ways to do more methodical cultures of these kinds of organoids, and especially to control the microenvironment."

The researchers have also shown that their new gel can be used to grow other types of tissue, including intestinal and endometrial tissue.

Griffith and Claus Jorgensen, a group leader at the Cancer Research UK Manchester Institute, are the senior authors of the paper, which appears today in Nature Materials. The lead author is Christopher Below, a former graduate student at the Cancer Research UK Manchester Institute.

Mimicking the microenvironment

Traditionally, labs have used commercially available tissue-derived gel to grow organoids in a lab dish. However, as the most widely used commercial gel is a complex mixture of proteins, proteoglycans, and growth factors derived from a tumor grown in mice, it is variable from lot to lot and has undesirable components present, Griffith says. It also doesn't always allow for growth of multiple types of cells. About 10 years ago, Griffith's lab started to work on designing a synthetic gel that could be used to grow epithelial cells, which form the sheets that line most organs, along with other supportive cells.

The gel they developed is based on polyethylene glycol (PEG), a polymer that is often used for medical applications because it doesn't interact with living cells. By studying the biochemical and biophysical properties of the extracellular matrix, which surrounds organs in the body, the researchers were able to identify features they could incorporate into the PEG gel to help cells grow in it.

One key feature is the presence of molecules called peptide ligands, which interact with cell surface proteins called integrins. The sticky binding between ligands and integrins allows cells to adhere to the gel and form organoids. The researchers found that incorporating small synthetic peptides derived from fibronectin and collagen in their gels allowed them to grow a variety of epithelial tissues, including intestinal tissue. They showed that supportive cells called stromal cells, along with immune cells, can also thrive in this environment.

In the new study, Griffith and Jorgensen wanted to see if the gel could also be used to support the growth of normal pancreatic organoids and pancreatic tumors. Traditionally, it has been difficult to grow pancreatic tissue in a manner that replicates both the cancerous cells and the supporting environment, because once pancreatic tumor cells are removed from the body, they lose their distinctive cancerous traits.

Griffith's lab developed a protocol to produce the new gel, and then teamed up with Jorgensen's lab, which studies the biology of pancreatic cancer, to test it. Jorgensen and his students were able to produce the gel and use it to grow pancreatic organoids, using healthy or cancerous pancreatic cells derived from mice.

"We got the protocol from Linda and we got the reagents in, and then it just worked," Jorgensen says. "I think that speaks volumes of how robust the system is and how easy it is to implement in the lab."

Other approaches they had tried were too complicated or did not recapitulate the microenvironment seen in living tissues, he says. Using this gel, Jorgensen's lab was able to compare the pancreatic organoids to tissues they have studied in living mice, and they found that the tumor organoids express many of the same integrins seen in pancreatic tumors. Furthermore, other types of cells that normally surround tumors, including macrophages (a type of immune cells) and fibroblasts (a type of supportive cells), were also able to grow in the microenvironment.

Patient-derived cells

The researchers also showed that they can use their gel to grow organoids from pancreatic cancer cells from patients. They believe it could also be useful for studying lung, colorectal, and other cancers. Such systems could be used to analyze how potential cancer drugs affect tumors and their microenvironment.

Griffith also plans to use the gel to grow and study tissue from patients with endometriosis, a condition that causes the tissue that lines the uterus to grow outside the uterus. This can lead to pain and sometimes infertility.

One of the advantages of the new gel is that it is completely synthetic, and can be made easily in a lab by mixing together specific precursors, including PEG and some polypeptides. The researchers have filed a patent on the technology and are in the process of licensing it to a company that could produce the gel commercially.

The research was funded by Cancer Research UK, the Rosetrees Trust, a European Research Council Consolidator Award, the National Science Foundation, the National Institutes of Health, and the Defense Advanced Research Projects Agency.

Source: ScienceDaily

Cancer cells’ unexpected genetic tricks for evading the immune system

 Hundreds of cancer-linked genes play a different role in causing disease than scientists had expected.

So-called tumor suppressor genes have long been known to block cell growth, preventing cancerous cells from spreading. Mutations in these genes, scientists believed, thus allow tumors to flourish unchecked.

Now, Howard Hughes Medical Institute Investigator Stephen Elledge's team has uncovered a surprising new action for many of these defective genes. More than 100 mutated tumor suppressor genes can prevent the immune system from spotting and destroying malignant cells in mice , Elledge, a geneticist at Brigham and Women's Hospital, reports September 16, 2021, in the journal Science. "The shock was that these genes are all about getting around the immune system, as opposed to simply saying 'grow, grow, grow!'" he says.

Conventional wisdom had suggested that, for the vast major of tumor suppressor genes, mutations allow cells to run amok, growing and dividing uncontrollably. But that explanation had some gaps. For example, mutated versions of many of these genes don't actually cause rampant growth when put into cells in a petri dish. And scientists couldn't explain why the immune system, which is normally highly proficient at attacking abnormal cells, doesn't do more to nip new tumors in the bud.

Elledge's newpaper offers some answers. His team probed the effects of 7,500 genes, including genes known to be involved in human cancer. A third or more of those cancer-linked genes, when mutated, trigger mechanisms that prevent the immune system from rooting out tumors, often in a tissue-specific manner.

"These results reveal a fascinating and unexpected relationship between tumor suppressor genes and the immune system," says HHMI Investigator Bert Vogelstein, a cancer geneticist at the Johns Hopkins University who was not involved in the research.

Wiping out melanoma

The idea that tumors can evade the body's defenses is not new, of course. In one major advance in cancer treatment over the last few decades, scientists figured out that some tumors churn out proteins that switch off immune cells known to attack cancerous cells. Pharmaceutical companies developed drugs, dubbed checkpoint inhibitors, that block those proteins and hyper-activate the immune system. The first checkpoint inhibitor, based on Nobel Prize-winning work by HHMI Alumnus James Allison at the University of California, Berkeley, was approved in 2011. Since then, the drugs have racked up some spectacular successes. In a high-profile case in 2015, a checkpoint inhibitor unleashed former President Jimmy Carter's immune system, letting it wipe out the melanoma that had spread to his brain.

Checkpoint inhibitors are now big sellers. But they aren't the overwhelming and universal therapy that some scientists had hoped for. In addition to having serious side effects, the drugs work only in a minority of patients and cancer types. Elledge's work helps explains why: in short, tumors have far more genetic tricks for fighting off the immune system than anyone had previously thought.

CRISPR engineering

Elledge had a hunch that defective tumor suppressor genes were doing something more than ramping up cell growth. Starting with a list of 7,500 genes, his team used CRISPR to engineer thousands of tumor cells. Each lacked a functioning version of one of those genes. The researchers put the cells into two types of mice: those with an immune system, and those without. Then, the team studied the tumors that grew.

Genetic analyses revealed which mutated genes were abundant in the tumors -- and likely playing a role in tumor formation. In mice with immune systems, defective tumor suppressor genes showed up frequently. This shows that those genes - about 30 percent of all tumor suppressor genes tested -- work by enabling tumors to evade the immune system, Elledge says.

Elledge's method revealed the many different genes that tumors can mutate to escape the body's defenses. To explore possible mechanisms triggered by the mutations, the researchers zeroed in on a gene called GNA13. Mutating the gene protects cancer cells from the immune system's T-cells, creating a safe space for the tumor to thrive, the team found.

Their research paints a sobering picture of a quick and fierce evolutionary arms race between cancer cells and the immune system, Elledge says, with tumors having hundreds of potential ways to foil the body's attack. But he suspects that many of these mutated genes act via similar strategies, a possibility his team can now examine in detail. If this proves to be the case, an intervention to block one evasion technique could potentially thwart others as well.

Overall, Elledge hopes his findings open new doors to treating cancer -- by making it possible to uncover and stymie tumors' new and different tricks. "There are a lot of genes that people can now study," he says.

Source: ScienceDaily

Can fruit fly research help improve survival of cancer patients?

 The experience of a fruit fly dying from cancer may seem worlds away from that of a human with a life-threatening tumor, yet University of California, Berkeley, researchers are finding commonalities between the two that could lead to ways to prolong the lives of cancer patients.

Fruit fly research is already pointing to a new anti-cancer strategy distinct from the conventional goal of destroying the tumor or cancerous cells. Instead, the research suggests, launching an attack against the destructive chemicals the cancer is throwing off could increase survival rates and improve patients' health.

"It's a really complementary way of thinking about therapy," said David Bilder, UC Berkeley professor of molecular and cell biology. "You're trying to help the host deal with the effects of the tumor, rather than killing the tumor itself."

Jung Kim, a postdoctoral fellow in Bilder's lab, recently discovered that tumors in fruit flies release a chemical that compromises the barrier between the bloodstream and the brain, letting the two environments mix -- a recipe for disaster in numerous diseases, including infection, trauma and even obesity. In collaboration with the labs of UC Berkeley professors David Raulet and Kaoru Saijo, Kim and Bilder subsequently demonstrated that tumors in mice that release the same chemical, a cytokine called interleukin-6 (IL-6), also make the blood-brain barrier leaky.

More importantly, they were able to extend the lifespan of both fruit flies and mice with malignant tumors by blocking the effect of the cytokine on the barrier.

"The IL-6 cytokine is known to cause inflammation. What's new here is that this tumor-induced inflammation is actually causing the blood-brain barrier to open. If we interfere with that opening process but leave the tumor alone, then the host can live significantly longer and healthier with the same tumor burden," Bilder said.

IL-6 plays other important roles in the body, so to benefit cancer patients, scientists would have to find a drug that blocks its action at the blood-brain barrier without altering its effects elsewhere. But such a drug could potentially extend the life span and health span of human cancer patients, he said.

Six years ago, Bilder's team found that tumors in fruit flies also release a substance that blocks the effects of insulin, providing a potential explanation for the tissue wasting called cachexia that kills one-fifth of all cancer patients. That work is now being explored by numerous labs around the world.

One advantage of helping the host fend off a tumor's effects on tissues far from the tumor site is that it could potentially reduce or even eliminate the need for toxic drugs typically used to subdue tumors. Such drugs also harm the patient, killing healthy cells as well as cancerous cells.

Beyond these side effects, targeting tumor cells "also selects for resistance in the tumor, because the tumor has genetic variability -- a drug-resistant clone arises that will then cause cancer recurrence," he said. "But if you could target the host cells, they have a stable genome and are not going to gain resistance to these drugs. That's our goal: to understand the ways that the tumor is affecting the host and attack the host side of the tumor-host dialogue."

Bilder and his colleagues published their work on IL-6 disruption of the blood-brain barrier last week in the journal Developmental Cell, and he authored a review of the impact that fruit fly research has had on understanding tumor-host interactions that was published last month in the journal Nature Reviews Cancer. Their cachexia work appeared in 2015 in Developmental Cell.

What actually kills cancer patients?

According to Bilder, scientists still are uncertain what causes death in many cancer patients. Cancer of the liver, for example, clearly destroys the function of an organ essential for life. However, other organs, like the skin or the ovaries, are less critical, yet people die from cancer in these sites, too, sometimes very quickly. And though cancers often metastasize to other organs -- multiple organ failure is one of the main causes of cancer death listed by doctors -- Bilder questions if that's the whole story.

"Many human cancers are metastatic, but that doesn't change the basic question: Why does the cancer kill?" he said. "If your tumor metastasized to the lung, are you dying because of lung failure or are you dying from something else?"

For that reason, he works with non-metastatic tumors implanted in fruit flies and mice and looks for systemic effects, not merely the effects on the tumor-containing organ itself.

One systemic effect of cancer is cachexia, the inability to maintain weight, which leads to wasting of muscle even when the patient is receiving intravenous nutrition. While Bilder discovered one possible reason for this -- cancers release a chemical that prevents insulin from storing energy in the body -- other scientists have found additional substances released by cancers that may also be responsible for tissue wasting.

Like cachexia, breaches in the blood-brain barrier may be another long-distance effect of tumors. In the new study, the researchers found that blocking the activity of IL-6 at the blood-brain barrier increased the lifespan of flies with cancer by 45%. Laboratory mice must be euthanized before they suffer and die from experimental cancer, but the team found that after 21 days, 75% of cancer-carrying mice treated with an IL-6 receptor blocker were alive, versus only 25% of untreated mice with cancer.

"It's not just the breakdown of the blood-brain barrier that's killing the animals," Bilder said. "Flies can live for three or four weeks with a leaky blood-brain barrier, whereas, if they have a tumor, they die almost immediately when the barrier is compromised. So, we think that the tumor is causing something else to happen. Maybe it's putting something in circulation that then gets through the broken barrier, though it could also be something going the other way, from the brain into the blood."

Bilder has found additional cancer-produced chemicals in flies that he's linked to edema -- bloating from excess fluid retention -- and excess blood clotting, which leads to blocked veins. Both conditions frequently accompany cancer. Other researchers have found tumor-produced fly chemicals linked to anorexia -- the loss of appetite -- and to immune disfunction, which also are symptoms of many cancers.

Bilder said that studying cancer in fruit flies offers several advantages over cancer models in other animals, such as mice and rats. For one thing, researchers can follow flies right up to the moment of death, in order to determine what actually causes mortality. Ethical concerns prevent researchers from allowing vertebrates to suffer, so research animals are euthanized before they die naturally, preventing a full understanding of the ultimate cause of death. For these animals, tumor size is used as a proxy to assess an animal's chance of survival.

"We're incredibly excited about the potential to look directly at survival and life span," he said. "We think that this is a real blind spot that hasn't allowed scientists to address questions about how the tumor is actually killing outside of its local growth. That's not to say that tumor size is misleading, but fruit flies give us a complementary way of looking at what cancer is doing."

And while most cancer studies in rodents involve just a few dozen animals, fruit fly experiments can involve many hundreds of individuals, which improves the statistical significance of the results. Fruit flies also reproduce quickly and have short natural life spans, allowing quicker studies.

Bilder acknowledges that fruit flies and humans are only distantly related, but in the past, these flies -- Drosophila melanogaster -- have played a key role in understanding tumor growth factors and oncogenes. Fruit flies now could also be key in understanding cancer's systemic effects.

"Not only can flies get tumors that resemble human tumors, which we described 20 years ago, but we're now seeing that the host response has remarkable similarities in cachexia, coagulopathies, immune response, cytokine production, all of these things," he said. "I think it (the tumor-host response in fruit flies) is a superrich area. Our hope is to bring attention to the field and attract other people to work in it, both from the fly perspective and from the cancer biology and clinician perspective."

Source: ScienceDaily

Getting the first dose of COVID-19 vaccine boosts mental health

 

• The COVID-19 pandemic has resulted in a significant rise in mental distress around the world.
• A recent study in the United States concludes that getting the first dose of the COVID-19 vaccine significantly improved mental health.
• Specifically, the researchers investigated the link between receiving a shot of the COVID-19 vaccine and short-term improvements in mental health.
• The results may help explain how pandemic-related stressors exacerbate mental health distress and how vaccines help out.

The COVID-19 pandemic has disturbed vital aspects of people’s lives — finances, work, socialization — potentially affecting their mental health. This resulted in an increase in mental distress in people in many countries of the world.

One study shows that levels of mental distress went up in the U.S. around March 2020 and only returned to pre-pandemic levels in August 2020.

ResearchersTrusted Source attribute this trend to various factors, including fear about the pandemic’s impact on the economy, concerns over the rising number of COVID-19 cases, and physical distancing measures.

With the rollout of the COVID-19 vaccines, a group of scientists embarked on a study to compare mental health improvements in people who received a vaccine with the improvements in those who did not. The results appear in the journal PLOS ONETrusted Source.

The scientists conclude that “getting the first dose of COVID-19 [vaccine] resulted in significant improvements in mental health, beyond improvements already achieved since mental distress peaked in the spring of 2020.”

Lead study collaborator, Dr. Francisco Perez-Arce, an economist at USC in Washington, described the study, which began in March 2020, to Medical News Today.

“Very early on in the pandemic, in March of 2020, we started a panel to track the multiple impacts of the pandemic on several outcomes, including mental health. Our panelists, who are respondents from the Understanding America Study, answered surveys every 2 weeks or so, which has allowed us to track trajectories in many variables, such as mental health and vaccination status,” he said.

“Looking at the impact of getting vaccinated allows us to study the extent to which reducing your health risks relieves mental distress,” he concluded.

Surveying mental distress and vaccination status

Dr. Perez-Arce and his colleagues surveyed 8,003 adult participants between March 10, 2020, and March 31, 2021.

They asked the participants, selected from the Understanding America Study (UAS), which is a nationally representative longitudinal study of Americans aged 18 years or older, to complete at least two study waves.

The participants answered questions about their COVID-19 vaccine status and self-reported mental distress levels, which the researchers then measured using the four-item Patient Health Questionnaire (PHQ-4)Trusted Source.

Between April 1, 2020, and February 16, 2021, the study authors measured the responses every 2 weeks. After that period, they measured them every 4 weeks. Altogether, the total data consisted of about 157,227 respondent-wave observations.

Interpreting the results

The study authors analyzed the data using two parameters: mental distress levels and vaccination status.

They measured the distress levels with the help of the PHQ-4 questionnaire, which uses two items each to measure depressive and anxiety symptoms, respectively.

They graded responses to each section between 0 and 4 and then summed them to create an index range between 0 and 16. Higher numbers on the scale corresponded with higher levels of mental distress.

Starting from December 2020, the respondents answered whether they had received their first shot of the COVID-19 vaccine. Based on the answers, the scientists assigned the participants specific values.

They used these values to compare the mental health trajectory of the people who received a vaccine at some point during the study with the mental health trajectory of those who never received a vaccine.

The results show that both groups had a similar direction until December 2020, when the first vaccine became available. After that point, there was a noticeable difference in baseline levels of mental health in both groups.

This led the researchers to conclude that there are short-term direct effects of getting the first vaccine shot.

Furthermore, they note that the effect the vaccines have on mental health spreads to others. They explain, “An unvaccinated individual may still benefit from the reduced prevalence rates in the population, may become less worried about loved ones, and may benefit from increased social and economic opportunities.”

Sara Makin, founder and CEO of Makin Wellness, an online mental health counseling service, shares this sentiment.

Makin said to MNT, “It may be useful for the public to note that the vaccine has not only eased mental distress for those who have received the vaccine but also for those who have not received the vaccine.”

Additionally, Makin told MNT that, despite improvements in mental distress associated with the vaccine, not everyone feels better. “For many people, returning to the ‘new normal’ is still a scary thought, and [their fears] are completely valid.”

More work necessary

Although the research is positive news, it is not without its limitations.

For instance, the researchers explain that sorting differences might have played a part. In other words, people with lower risk of developing depression may have been more likely to decide to get a vaccine.

The authors hope that future research might dig a little deeper into these findings to understand why they observed this reversal of mental distress.

Source: Medical News Today

COVID-19 vaccines: Effective in preventing hospitalization and ER visits

 

• Vaccines against COVID-19 were available to the public about 1 year after the pandemic began.
• Three vaccines are currently in use in the United States: the Moderna, Pfizer-BioNTech, and Johnson & Johnson vaccines.
• A new study shows that these vaccines are highly effective in preventing hospitalizations and emergency room (ER) visits.

The COVID-19 pandemic continues to influence hospital systems all over the world. The Centers for Disease Control and Prevention (CDC) are continuing to try to track the number of cases of COVID-19 and the deaths resulting from it in the U.S.

In the U.S., there have been more than 41 million cases of COVID-19 and in excess of 660,000 related deaths.

Since vaccines against COVID-19 became available, experts have been researching their overall effectiveness in preventing severe cases of COVID-19.

This research includes looking at hospitalization rates and ER visits among individuals who have received vaccination against COVID-19.

A recent study, which appears in the New England Journal of Medicine, suggests that full mRNA vaccination — two doses — against COVID-19 is 89% effective in preventing hospitalizations related to the disease.

Vaccine development

Scientists started developing vaccines against SARS-CoV-2, the virus that causes COVID-19, shortly after the start of the pandemic. However, researchers had been investigating vaccines for coronaviruses in general for years before this.

The Food and Drug Administration (FDA) approved the Pfizer-BioNTech vaccineTrusted Source, also called BNT162b2, for emergency use in December of 2020. The Moderna vaccineTrusted Source, also called mRNA-1273, received similar authorization around the same time. These are both mRNA vaccines, and both require two shots for full vaccination.

In addition to these, there is also Johnson & Johnson’s JanssenTrusted Source vaccine, or the Ad26.COV2.S vaccine, which is a single dose vaccine.

Currently, about 75% of the U.S. population have received at least one vaccine dose. Research is ongoing regarding vaccine effectiveness in minimizing the severity of SARS-CoV-2 infections.

As the authors explain, placebo-controlled phase 3 trials of these three vaccines and observational studies of the mRNA vaccines have already demonstrated that they are “highly effective in preventing symptomatic COVID-19.”

However, the authors also write that “less is known about how well these vaccines protect against more severe illness due to [SARS-CoV-2] resulting in hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic.”

Vaccine effectiveness

To investigate, the current study investigated the effectiveness of vaccines in preventing severe symptoms of COVID-19. Specifically, they examined:

• hospitalizations
• stays in ICUs
• ER or urgent care clinic visits

The researchers collected data from January 1 through June 22, 2021, from 187 hospitals in multiple states. The study included adults aged 50 years and older. The researchers’ data included 41,552 hospital admissions and 21,522 visits to either ERs or urgent care clinics.

The data also included the vaccination status of the participants, including the number of doses and how long it had been since they received their doses.

The researchers accounted for the age of each participant, as well as their geographic region, the time frame of vaccination and, the local circulation of the virus. They used this information to assess the effectiveness of COVID-19 vaccines.

Discussing their methods, the authors write, “We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients.”

Their results showed that the vaccines were highly effective in preventing hospitalizations, stays in the ICU, and ER visits related to COVID-19. The results included the following highlights:

• The mRNA vaccines — Moderna and Pfizer–BioNTech — were 89% effective in preventing hospitalization in confirmed positive cases of a SARS-CoV-2 infection.
• Both Moderna and Pfizer–BioNTech were 90% effective in preventing ICU admissions and 91% effective in preventing ER or urgent care visits.
• The Johnson & Johnson vaccine was 68% effective in preventing hospitalization and 73% effective in preventing ER or urgent care visits.

The researchers also found that vaccines were highly effective among groups whom the virus disproportionately affects, including people aged 85 years or older, Black and Hispanic adults, and individuals with chronic respiratory diseases.

Study author Dr. Shaun Grannis told Medical News Today that this study and other research represent “our initial efforts using real world data from actual patients to develop a solid evidence base for the effectiveness of COVID-19 vaccines.” He continued:

“Evidence of this nature is crucial to understanding the impact of the vaccines on the pandemic and to providing information to public health experts and people who are unsure about receiving the vaccine.”

Further vaccine research

The study, which the CDC supported, did have some limitations. The authors note the potential for bias and acknowledge that their analysis could not account for all influential factors.

For example, they did not take into account exposure risk based on factors such as profession. Some professions had access to vaccinations and personal protective equipment, whereas others did not.

However, they attempted to account for this by not beginning data collection until the vaccines were available to the general public.

Also, they took data from several different hospitals and clinical settings. The researchers note that the policies for testing for SARS-CoV-2 may vary among hospitals based on vaccination status. There was a risk of both over and underestimation of vaccine efficiency.

Importantly, based on the time frame of the study, the researchers were not able to determine vaccine efficacy against the delta variant.

In response to being asked to comment on the study, Dr. David W. Dowdy, an epidemiology specialist with Johns Hopkins University, was eager about the study’s results. He told MNT:

“[The study] provides robust scientific evidence that the vaccines in use in the U.S. — and particularly the Pfizer and Moderna vaccines — provide strong, consistent protection again SARS-CoV-2 infection that is serious enough to seek care in an urgent care or an emergency department.”

“In every population the authors tested, full vaccination provided [greater than] 80% protection — regardless of age, race, geographic location, or other medical conditions,” he continued.

He further emphasized that continued research could focus efforts on investigating the waning immunity of COVID-19 vaccines:

Overall, this study represents continued efforts in data collection regarding vaccines for COVID-19. It demonstrates high levels of vaccine effectiveness, particularly among those whom the SARS-CoV-2 virus is most likely to affect.

Source: Medical News Today

High levels of stress hormones may raise risk of hypertension, cardiovascular disease

 

• The body’s hormonal response to experiencing stress is a natural function that humans and animals have in common.
• Excessive levels of stress hormones, such as norepinephrine, epinephrine, dopamine, and cortisol can adversely affect people’s health.
• A new study suggests that higher levels of stress hormones may have links to an increased risk of high blood pressure and cardiovascular events.

Scientists have studied how the body responds to its environment for years. Stress Trusted Sourceis the result of pressures or tensions and how the body responds to them. StressorsTrusted Source lead to a change in the body’s normal state, causing it to respond in several different ways. These changes, which are called the stress response, include the release of certain hormones.

Scientists are still exploring the effect of this stress response and the overall impact of stress on long-term health complications.

A new study published in Hypertension, an American Heart Association journal, shows mounting evidence that higher levels of stress hormones may increase a person’s risk of high blood pressure and cardiovascular events.

Stress hormones and the impact of stress

The body’s stress response is complex and involves multiple hormones, including cortisol. The adrenal glands produce cortisol, which increases energy levels and helps the body react during emergencies.

Stress also plays a role in the release of catecholamines. Examples of catecholamines include dopamine, epinephrine, and norepinephrine (also known as adrenaline and noradrenaline, respectively).

Epinephrine and norepinephrine both play key roles in the body’s fight or flight response. When exposed to a perceived threat, the fight or flight response prepares the body to face or evade the danger.

Epinephrine and norepinephrine help to:

• constrict blood vessels to maintain blood pressure
• increase heart rate and the force with which the heart pumps blood to the rest of the body
• relax airway muscles
• control the metabolism of glucose

When a person is under stress, the body has higher levels of these hormones. While these stress responses can help short-term, longer-term stress or continued exposure to stress can cause health problems.

As noted by the American Heart Association, chronic stress may lead to high blood pressure, which increases a person’s risk of having a stroke or heart attack. Furthermore, when people experience stress, they may turn to unhealthy coping mechanisms that put them at risk for poor physical health.

This is partly why the American Heart Association has recently focused on stress reduction techniques as a vital component of overall health. In a recent Facebook post, they shared tips for stress reduction from Psychiatry Professor Dr. Helen Lavretsky.

Dr. Lavretsky emphasized how people can utilize several techniques for stress reduction, including looking for joyous moments throughout the day, finding things to be grateful for, and using slowed breathing techniques.

Scientists are still exploring the relationship between stress hormones and risks of cardiovascular problems, and the study in question offers further information.

Increased risk for high blood pressure and cardiovascular events

The research — carried out by scientists from the University of California in Los Angeles — is a prospective cohort study that examines the association between higher levels of stress hormones and increased risk of high blood pressure and cardiovascular events.

The study included 412 adults ages 48–87 years. Participants had no previous history of high blood pressure, which was one of the key differences between the current and previous studies. The study also involved a diverse mix of participants, including white, Black, and Hispanic individuals.

Researchers took into account the participants’ sex, education level, income, and health insurance status. They also examined their lifestyle factors, including whether they drank alcohol, smoked, and did any physical activity.

Finally, researchers looked at the health status of the participants, including whether they had diabetes, their use of any medications, body mass index, and kidney function.

This study was part of a larger study called the Multi-Ethnic Study of Atherosclerosis (MESA). At the start of the study, the researchers asked a subset of participants from the larger study with no diagnosed cardiovascular disease to participate in a 12-hour overnight urine collection. The researchers analyzed the urine for levels of epinephrine, norepinephrine, dopamine, and cortisol.

The researchers included participants who had no hypertension at baseline and had complete data and specific covariates in further data analysis.

Researchers followed up with participants for an average of 6.5 years to evaluate hypertension. During the years of follow-up, 48.8% of participants had developed high blood pressure. Over the average follow-up of 11.2 years, 5.8% of participants experienced cardiovascular events. Cardiovascular events included heart attacks, coronary heart disease death, stroke, and the development of peripheral vascular disease.

Using multivariable Cox proportional hazard models, researchers calculated the risk of high blood pressure and cardiovascular events associated with urinary stress hormones.

Results revealed that higher levels of stress hormones in the urine have associations with a greater risk of high blood pressure. The researchers found this association was stronger among younger individuals than among older individuals.

They further found that a double than normal level of urinary cortisol has associations with a higher incidence of cardiovascular events. They did not find an association between higher levels of catecholamines and cardiovascular events.

Study limitations and continuing research

The study accounted for several factors and included a diverse sample. However, researchers do acknowledge the study’s limitations. Due to the nature of the 12-hour overnight urine collection, there was the possibility for errors in specimen collection.

The authors also acknowledge the possibility of sample bias and unaccounted influencing factors. For example, their analysis method did not account for the stratified analysis of cardiovascular events. The researchers also did not differentiate the causes of the developed high blood pressure.

Considering these limitations and the small sample size of the study, researchers encourage the following when it comes to continued data collection in this area:

• continued long-term studies that look at urinary stress hormones and include larger sample sizes
• studies that do multiple measurements of urinary stress hormone levels
• studies that account for the causes of high blood pressure
• more inclusion of factors that can influence a study’s results

Overall, the results indicate the importance of taking psychological stress into account to create a holistic view of health and help prevent long-term complications. Professor of Medicine and cardiology specialist Dr. Glenn N. Levine told MNT:

Dr. Glenn, a Professor of Medicine at Baylor College of Medicine in Houston, Texas, and co-authored the study. MNT also reached out to Prof. Bernard Cheung, Ph.D., FRCP, Sun Chieh Yeh Heart Foundation Professor in Cardiovascular Therapeutics at the University of Hong Kong.

Prof. Cheung, who was not involved in the research, felt that the study findings were “interesting.” However, he said, people should interpret the results with caution.

“Firstly, association is not the same as causation. One should not jump to the conclusion that hypertension can be prevented by stress management,” Prof. Cheung said.

“Secondly, there is a phenomenon known as white coat hypertension. People with white coat hypertension are more nervous, and their blood pressure goes up when it is being measured. Thirdly, the study did not analyze men and women separately. Finally, it would have been better if [the researchers] had measured stress using a questionnaire to supplement the data from urinary hormones,” added the expert.

Source: Medical News Today

Obesity and weight loss: Why overall calorie intake may not be so important

 

• Conventional scientific opinion has attributed weight gain to a net surplus of calories due to burning fewer calories than taking in.
• Opposing this view, the carbohydrate-insulin model states that diet quality matters more for weight loss than total calorie intake.
• The model posits that the intake of processed carbohydrates and starchy foods leads to changes in the levels of insulin and other hormones, subsequently resulting in increased fat deposition.
• The increased fat deposits lead to hunger and consumption of more calorie-rich foods leading to obesity.
• The model suggests that avoiding processed carbohydrates and starchy foods may be necessary to lose weight instead of restricting calories.

The World Health Organization (WHO)Trusted Source states that the global prevalence of overweight and obesity has increased in the past 5 decades.

There is significant consensus in the scientific community that environmental factors, especially the easy availability of highly processed foods and sedentary lifestyles, have contributed to increasing obesity rates.

However, there is much disagreement about how these environmental factors contribute to weight gain.

According to the predominant energy balance model (EBM), consuming more calories than those burned results in a positive energy balance and weight gain.

The increased caloric intake due to the easy accessibility of highly palatable and inexpensive processed food and lower energy expenditure due to reduced physical activity levels have contributed to the global increase in obesity.

In other words, the EBM suggests that successful weight loss requires reducing total calorie intake. This involves consuming fewer calories and increasing physical activity levels.

Unlike the EBM, the carbohydrate-insulin model (CIM) posits that the quality of food consumed plays a critical role in body weight management rather than total calorie intake.

Specifically, consumption of processed and starchy carbohydrates that cause a rapid increase in blood glucose levels results in their storage as fat. Increased fat accumulation sets off a feedback loop resulting in increased hunger and possible consumption of calorie-rich foods.

The CIM states that it is the increase in fat storage due to the consumption of processed carbohydrates and not increased calorie intake that leads to weight gain and is primarily responsible for elevated obesity rates.

A recent article published in the American Journal of Clinical NutritionTrusted Source provides a comprehensive description of the CIM, along with testable hypotheses that may help clarify the precise changes in nutrition necessary to lose weight or maintain a healthy weight.

The article’s first author Dr. David Ludwig, told Medical News Today, “If the CIM is right, then the conventional approach to weight loss, the low-calorie diet, is likely to fail for most people over the long term. We argue that people have more control over what they eat than how much. A focus on reducing processed carbohydrates, rather than calorie restriction, may be more effective by lowering the biological drive to store excessive fat.”

Flaws of the EBM

According to the EBM, a positive energy balance where a person takes in more calories than they burn is primarily responsible for weight gain. In other words, the EBM regards all calories in the same way, regardless of their dietary source.

The proponents of the CIM acknowledge that a positive energy balance is associated with weight gain, but this does not establish causation.

They argue that metabolic and hormonal changes that occur in response to the consumption of specific foods are the root cause of weight gain, with excessive calorie intake being the outcome.

Although calorie intake tends to increase during puberty, some experts think that it is the biological changes rather than positive energy balance that is responsible for the growth spurt.

Therefore, while the EBM focuses on the overall consumption of calories, it ignores the role of food quality and the subsequent metabolic processes and hormonal changes in mediating weight gain.

Moreover, reducing caloric intake tends to be successful as a weight-loss strategy only in the short term. This is due to the body adapting to the lower calorie intake, resulting in lower metabolic rate and increased hunger.

The CIM

According to the CIM, food quality plays a more significant role in weight gain than overall calorie intake.

In addition to highly processed carbohydrates, the intake of carbohydrates has been increasing since the 1980s. This is likely due to the perception that consuming fats causes weight gain.

The glycemic index (GI) rates carbohydrates according to how rapidly they raise blood glucose levels after someone has eaten them. The glycemic load is another measure that provides more comprehensive information about the surge in blood sugar levels by considering the GI and amount of carbohydrates a serving of a given food provides.

Consumption of processed and starchy foods that contain rapidly digestible carbohydrates results in a surge in blood glucose levels. Foods with a high glycemic load include processed grains, potato products, and foods with high free sugarsTrusted Source content. Free sugars are all types of sugars that do not occur naturally in whole fruits and vegetables.

In contrast, fats and proteins have a negligible impact on blood sugar levels, whereas fresh whole fruits, minimally processed grains, legumes, nuts, and nonstarchy vegetables typically have a low or moderate glycemic load.

The rapid surge in glucose levels after consuming high glycemic load foods results in the secretion of insulin, which regulates blood sugar levels and helps the muscles, liver, and adipose or fat tissue absorb glucose.

At the same time, consuming rapidly digestible carbohydrates suppresses the levels of the hormone glucagon.

The pancreas secretes glucagon to counter low blood sugar levels that occur between meals. Glucagon secretion raises blood glucose levels by stimulating the release of glucose stored in the liver as glycogen.

During the first 3 hours after the intake of high glycemic load foods, high insulin and low glucagon levels lead to the storage of glucose as glycogen in the liver and as fat in the liver and adipose or fat tissue.

Although the body absorbs the nutrients present in high glycemic load foods in the initial 3–4 hours, the high insulin and low glucagon levels persist.

This hormonal state slows down the breakdown of the energy stores in the liver and adipose tissue needed to fuel critical tissues in the body. This results in low levels of glucose, fatty acids, and other metabolites in the blood, resembling a fast-like state.

The drop in blood metabolite levels signals the brain, indicating that the tissues are deprived of energy.

When the brain perceives this fast-like state, it provokes hormonal changes that lead to hunger and craving for high-energy foods, such as those high on the GI.

The consumption of foods with a high glycemic load leads to their accumulation as fat. This leads to a positive feedback loop, resulting in the consumption of more high glycemic load foods.

The fast-like state resulting from the consumption of high-glycemic load foods may also result in changes in the body that result in lower energy expenditure.

Addressing the scientific basis of the CIM, Dr. Ludwig said: “ There is strong evidence for some of these steps. For instance, in animals, it has been conclusively shown that all calories are not alike and that obesity can develop without increased food intake. There is evidence, but not yet proof, for this possibility in humans.”

Criticisms

The CIM has provoked a significant amount of controversy, including how insulin and carbohydrates affect weight gain.

Dr. Aaron Roseberry, associate professor at Georgia State University, told MNT, “I think there is going to be a lot of individual variability in the physiology and changes that occur in individuals with obesity as they [develop obesity]. There may be some role for insulin, along with a lot of other factors that may contribute different amounts in different individuals. This just makes it even more challenging to really identify the causes and potential treatments to help prevent weight gain and the development of obesity.”

Another criticism of the CIM is the absence of a significant difference in weight loss in some studies comparing individuals on a low carbohydrate diet with those on a low fat diet.

The authors contend that these results could be due to the long duration of these studies, during which participants may find it difficult to adhere to the dietary regimens. Furthermore, they point out that some evidence shows that a low carbohydrate diet can result in more weight loss than a low fat diet.

MNT spoke to Dr. Christopher Gardner, professor at Stanford University, CA. He is the lead author of one such studyTrusted Source comparing the impact of a healthy low fat diet versus a low carbohydrate diet.

Describing the study, Dr. Gardner said: “We very specifically looked at insulin secretion levels in the participants to differentiate the individuals in the study who were more likely to be insulin resistant vs. insulin sensitive. We had hypothesized that a healthy low carb diet would be more helpful for those who were more insulin resistant.”

“However, we found that weight loss was no different for healthy low carb vs. healthy low fat, even when taking insulin secretion (a proxy measure for insulin resistance) into account,” continued Dr. Gardner.

The authors argue that participants in the low fat diet group in this study eliminated carbohydrates with a high glycemic load, and hence, these results do not contradict their model.

MNT also spoke to Dr. Stephen Guyenet, the author of the book The Hungry Brain. Dr. Guyenet said, “This is the most detailed and persuasive articulation of their hypothesis to date. I support low carbohydrate diets as a valid option for bodyweight management. I think their model of obesity has substantial limitations, though.” Dr. Guyenet continued:

The authors acknowledge that although carbohydrates and insulin play a vital role in the model, other hormones and biological processes work in association with insulin to mediate the effects of increased consumption of high glycemic load foods.

The CIM also claims to reverse the conventional wisdom that excess intake of calories leads to weight gain and posits that increased fat accumulation due to metabolic and hormonal changes results in obesity.

However, Dr. Gardner noted that both the EBM and CIM might have some merit in terms of weight loss. In other words, there seems to be a bidirectional relationship between food intake and metabolic changes.

“I also find the claim that the CIM represents a reversal in the causal pathway to be problematic. […] I find those types of statements to be more damaging than helpful in trying to clear up confusion around nutrition topics,” said Dr. Gardner.

Implications

In line with their model, the authors recommend that a person is more likely to achieve long-term weight loss by modifying diet quality rather than reducing total calorie intake.

“Trying to count calories (adding those you’ve eaten, and subtracting those that you may have burned in physical activity) is fraught with challenges in terms of accuracy, and this can be easily “gamed” so that people think they are doing the right thing, but they really are not accurately assessing these two components […] leading to poor results,” added Dr. Gardner.

The authors suggest that adhering to a diet consisting of low GI foods can lead to weight loss by reducing hunger and increasing energy levels. 

Dr. Gardner warned that dietary advice recommending strict low carbohydrate intake sometimes involves a limited intake of healthy carbohydrates.

He said, ”I feel that a shortcoming is when this gets carried over into avoiding legumes (beans, lentils, pulses, etc.), whole fruits, and whole grains. Those are carbohydrate-rich food groups that the Dietary Guidelines for Americans, the American Heart Association, the American Cancer Society, the World Health Organization, and the Food and Agriculture Organization of the United Nations recommend. Those are the sources of good quality carbohydrates (low GI and good sources of fiber). I think recommending limiting those food sources is dangerous and will have adverse health consequences.”

Moving beyond controversies

The arguments about the validity of the CIM and the EBM have been divisive and adversarial.

“The field of obesity should embrace paradigm clash as an essential step forward. Toward this end, investigators should, first, refrain from hyperbolic claims to have disproven (or proven) alternative explanations of the obesity pandemic,” suggest the authors.

The authors also recommend “collaborations among scientists with diverse viewpoints to test predictions in rigorous and unbiased research and […] depersonalize the debate, scrupulously avoiding ad hominem argument. Rigorous research using complementary designs will be needed to resolve the debate, clarify a middle ground, or point the way to new explanatory models that better encompass the evidence.”

While there is substantial disagreement in the scientific community, there seems to be an agreement regarding the need to reduce the consumption of processed food.

Dr. Gardner noted, “I would like to see proponents of both EBM and CIM get together and make it clear that there is substantial agreement on reducing the intake of added sugars and refined grains in the diet as a major priority for addressing the obesity epidemic. I believe hearing this kind of agreement would be very beneficial for the public who is understandably confused.”

“If you want to dive into insulin secretion/resistance, fuel partitioning, ultra-processed vs. unprocessed, basal metabolic rate, lean vs. adipose tissue, ad libitum vs. isocaloric […] we can continue to discuss what small differences we might find around the periphery or fringe that could help some people to fine-tune their eating behaviors […].”

Source: Medical News Today