Publisher Health

Stem cell biologist Hugo Vankelecom (KU Leuven) and his colleagues have discovered that the pituitary gland in mice ages as the result of an age-related form of chronic inflammation. It may be possible to slow down this process or even partially repair it. The researchers have published their findings in PNAS.
The pituitary gland is a small, globular gland located underneath the brain that plays a major role in the hormonal system, explains Professor Hugo Vankelecom from the Department of Development and Regeneration at KU Leuven. “My research group discovered that the pituitary gland ages as a result of a form of chronic inflammation that affects tissue and even the organism as a whole. This natural process usually goes unnoticed and is referred to as ‘inflammaging’ — a contraction of inflammation and ageing. Inflammaging has previously been linked to the ageing of other organs.” Due to the central role played by the pituitary, its ageing may contribute to the reduction of hormonal processes and hormone levels in our body — as is the case with menopause, for instance.
The study also provides significant insight into the stem cells in the ageing pituitary gland. In 2012, Vankelecom and his colleagues showed that a prompt reaction of these stem cells to injury in the gland leads to repair of the tissue, even in adult animals. “As a result of this new study, we now know that stem cells in the pituitary do not lose this regenerative capacity when the organism ages. In fact, the stem cells are only unable to do their job because, over time, the pituitary becomes an ‘inflammatory environment’ as a result of the chronic inflammation. But as soon as the stem cells are taken out of this environment, they show the same properties as stem cells from a young pituitary.”
Chance of recovery?
This insight opens up a number of potential therapeutic avenues: would it be possible to reactivate the pituitary? This wouldn’t just involve slowing down hormonal ageing processes, but also repairing the damage caused by a tumour in the pituitary, for example. “No fewer than one in every 1,000 people is faced with this kind of tumour — which causes damage to the surrounding tissue — at some point. The quality of life of many of these patients would be drastically improved if we could repair this damage. We may be able to do so by activating the stem cells already present — for which our present study also provides new indications — or even by transplanting cells. That said, these new treatment options are not quite around the corner just yet, as the step from fundamental research to an actual therapy can take years to complete. For the time being, our study sets out a potential direction for further research.”
The study also suggests another interesting avenue: the use of anti-inflammatory drugs to slow down pituitary ageing or rejuvenate an ageing pituitary. “Several studies have shown that anti-inflammatory drugs may have a positive impact on some ageing organs. No research has yet been performed on this effect in relation to the pituitary.”
From mice to humans
Vankelecom and his colleagues studied the pituitary of mice, so further research is required to demonstrate whether their findings also apply to humans. Vankelecom comments: “Mice have a much greater regeneration capacity than humans. They can repair damaged teeth, for instance, while humans have lost this ability over the course of their evolution. Regardless, there are plenty of signs suggesting that pituitary processes in mice and humans are similar, and we have recent evidence to hand that gene expression in the pituitaries of humans and mice is very similar. As such, it is highly likely that the insights we gained will equally apply to humans.”
Story Source:
Materials provided by KU Leuven. Original written by Katrien Bollen. Note: Content may be edited for style and length.

Scientists have identified how and why some Covid-19 patients can develop life-threatening clots, which could lead to targeted therapies that prevent this from happening.
The work, led by researchers from RCSI University of Medicine and Health Sciences, is published in the Journal of Thrombosis and Haemostasis.
Previous research has established that blood clotting is a significant cause of death in patients with Covid-19. To understand why that clotting happens, the researchers analysed blood samples that were taken from patients with Covid-19 in the Beaumont Hospital Intensive Care Unit in Dublin.
They found that the balance between a molecule that causes clotting, called von Willebrand Factor (VWF), and its regulator, called ADAMTS13, is severely disrupted in patients with severe Covid-19.
When compared to control groups, the blood of Covid-19 patients had higher levels of the pro-clotting VWF molecules and lower levels of the anti-clotting ADAMTS13. Furthermore, the researchers identified other changes in proteins that caused the reduction of ADAMTS13.
“Our research helps provide insights into the mechanisms that cause severe blood clots in patients with Covid-19, which is critical to developing more effective treatments,” said Dr Jamie O’Sullivan, the study’s corresponding author and research lecturer within the Irish Centre for Vascular Biology at RCSI.
“While more research is needed to determine whether targets aimed at correcting the levels of ADAMTS13 and VWF may be a successful therapeutic intervention, it is important that we continue to develop therapies for patients with Covid-19. Covid-19 vaccines will continue to be unavailable to many people throughout the world, and it is important that we provide effective treatments to them and to those with breakthrough infections.”
This work was funded by Irish COVID-19 Vasculopathy Study (ICVS) through the Health Research Board COVID-19 Rapid Response award as well as a philanthropic grant from the 3M Foundation to RCSI University of Medicine and Health Sciences in support of COVID-19 research.
Story Source:
Materials provided by RCSI. Note: Content may be edited for style and length.

New research led by the University of Kent has found that there is no link between bed sharing, infant-mother attachment, and infant behavioural outcomes.
Contrary to previous beliefs that bed sharing is beneficial (or even required) for babies to develop a secure attachment style and for mothers to develop a strong bond to their baby, researchers have found that it is neither associated with positive or negative outcomes related to infant attachment and maternal bonding.
There is a lot of controversial debate about bed sharing by parents and the infant sleep literature, in particular. Notably, researchers and practitioners recommend against bed sharing, particularly before four months of age due to the increased risk of Sudden Infant Death Syndrome (SIDS).
In reality, parents quite often share their bed with their baby due to several reasons such as practicality and breastfeeding, or because they follow the idea of ‘attachment parenting’.
The research paper, published by the Journal of Developmental & Behavioral Pediatrics, analyses data from 178 infants and their parents, at term, three, six and eighteen months. No associations between bed sharing during the first six months and infant-mother attachment and infant behavioural outcomes (attention levels/hyperactivity and task persistence) at eighteen months were found. Similarly, there were no associations between bed sharing during the first six months and maternal bonding and sensitivity in interacting with the infant at consequent assessment points.
This new study, led by Dr Ayten Bilgin (Kent’s School of Psychology) alongside Professor Dieter Wolke, Professor of Developmental Psychology and Individual Differences at the University of Warwick concludes that longer follow-up studies on effects on child development may be required.
Dr Bilgin said: ‘A lot of people think that bed sharing is necessary to promote secure attachment with infants. However, there is little research in this area and quite mixed evidence. More insight into the outcomes of bed sharing is required to better inform parents, guardians and practitioners.’
Professor Wolke said: ‘Around a third of all parents share their bed with their infant during the first 18 months of life occasionally to most nights in this UK study. We found the practice was associated with ease of breastfeeding and dealing with night waking of the baby.’
Story Source:
Materials provided by University of Kent. Original written by Olivia Miller. Note: Content may be edited for style and length.

In the heart there are two different subtypes of beta-adrenergic receptors — beta1 and beta2 — which are activated by the stress hormones adrenaline and noradrenaline. They both trigger the strongest stimulation of the heart rate and pumping capacity that we know of. The two subtypes are highly similar biochemically, but differ substantially in terms of their functional and therapeutic relevance.
Both receptor types can stimulate the heart in the short term, yet when the beta1 receptor is activated over a prolonged period of time, it has a range of effects that are not seen with beta2. Beta1 can elicit a number of persistent changes and is endowed with the ability to initiate — oftentimes detrimental — growth of the heart muscle cells by activating various genes.
Recent studies by researchers at the Universities of Würzburg and Erlangen, the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) in Berlin, and the ISAR Bioscience Institute in Munich-Planegg have now shed light on the mechanisms behind these different effects. The research teams have published the results of their work in the current issue of the journal Proceedings of the National Academy of Sciences.
Special ligands and new microscopy methods
“Using a fluorescent ligand synthesized at the University of Erlangen and novel highly sensitive microscopy methods, we were able to show for the first time where these receptors are located on heart muscle cells,” explains Professor Martin Lohse of the Institute of Pharmacology and Toxicology at the Julius Maximilians University of Würzburg (JMU). He is co-lead author of the study along with Dr. Paolo Annibale, who is acting head of the MDC’s Receptor Signaling Lab. “The endogenous receptors are expressed at relatively low levels,” explains Annibale. “To detect their movement, it was necessary to use a form of spectroscopy based on the analysis of the signal’s minute fluorescence fluctuations.”
This revealed that beta1 receptors are found on the entire surface of heart muscle cells, while beta2 receptors are exclusively found in specific structures in these cells called T-tubules. Through invaginations of the cell surface, these tubules create a pipe-like network that runs through the entire interior of heart muscle cells. “One of the research focuses of our team at the MDC is the relationship between receptor function and subcellular localization,” adds Annibale. “So the biophysical environment of T-tubules, which have curved membranes, is of particular interest to us.”
Not all heart muscle cells have beta1 receptors
“The specific cellular location of beta2 receptors explains why they have a much narrower range of functionality than beta1 receptors and why they are limited to direct and short-term stimulation of the heart,” explains Lohse. Such stimulation is mediated by signals that are locally restricted to the cell membrane. In contrast, gene activation and cell growth stimulation occur via more far-reaching signals that can only be triggered at the cell surface, where only beta1 receptors are located.
Another surprising finding of the study is that not all heart muscle cells have these receptors. “There are apparently different types or states of heart muscle cells, so not all cells respond to adrenaline,” Lohse said. Until now, it was assumed that heart muscle cells in the large chambers were all the same.
New target for heart failure therapy
It has been known for many years that in chronic heart failure, too much adrenaline and noradrenaline circulate in the bloodstream and stimulate the heart to such an extent that it causes changes in the heart and its cells to grow. This initially compensates for heart failure, but in the long run the excessive growth damages the heart. Therefore, based in part on earlier findings by the Würzburg team, blocking beta receptors has become the accepted therapy for chronic heart failure.
The new findings now show why beta1 receptors play a much greater role in producing these adverse effects than beta2 receptors. Beta1 receptors are localized on the entire cell surface, enabling them to have a more diverse impact than beta2 receptors. The new knowledge about the differential localization and distinct functional effects of beta1 and beta2 receptors in the heart could possibly be exploited to develop better therapies for chronic heart failure. These would selectively inhibit the harmful effects of beta receptors (such as heart muscle cell growth), while at the same time activating the beneficial effects (such as stimulation of heart function).
Story Source:
Materials provided by University of Würzburg. Original written by Gunnar Bartsch. Note: Content may be edited for style and length.

A new antibody testing study examining samples originally collected through the National Institutes of Health’s All of Us Research Program found evidence of SARS-CoV-2 infections in five states earlier than had initially been reported. These findings were published in the journal Clinical Infectious Diseases. The results expand on findings from a Centers for Disease Control and Prevention study that suggested SARS-CoV-2, the virus that causes COVID-19, was present in the U.S. as far back as December 2019.
In the All of Us study, researchers analyzed more than 24,000 stored blood samples contributed by program participants across all 50 states between Jan. 2 and March 18, 2020. Researchers detected antibodies against SARS-CoV-2 using two different serology tests in nine participants’ samples. These participants were from outside the major urban hotspots of Seattle and New York City, believed to be key points of entry of the virus in the U.S. The positive samples came as early as Jan. 7 from participants in Illinois, Massachusetts, Mississippi, Pennsylvania and Wisconsin. Most positive samples were collected prior to the first reported cases in those states, demonstrating the importance of expanding testing as quickly as possible in an epidemic setting.
“This study allows us to uncover more information about the beginning of the U.S. epidemic and highlights the real-world value of longitudinal research in understanding dynamics of emerging diseases like COVID-19,” said Josh Denny, M.D., M.S., chief executive officer of All of Us and an author of the study. “Our participants come from diverse communities across the U.S. and give generously of themselves to drive a wide range of biomedical discoveries, which are vital for informing public health strategies and preparedness.”
In studies like these, false positives are a concern, particularly when the prevalence of viral infections is low, as was the case in the early days of the U.S. epidemic. Researchers in this study followed CDC guidance to use sequential testing on two separate platforms to minimize false positive results.
All of Us worked with Quest Diagnostics to test samples on the Abbott Architect SARS-CoV-2 IgG ELISA and the EUROIMMUN SARS-CoV-2 ELISA (IgG) platforms. For a sample to be considered “positive” by the research team, it had to have positive results on both platforms, which target antibodies that bind to different parts of the virus. Both tests have emergency use authorization from the FDA.
“Antibody testing of blood samples helps us better understand the spread of SARS-CoV-2 in the U.S. in the early days of the U.S. epidemic, when testing was restricted and public health officials could not see that the virus had already spread outside of recognized initial points of entry,” said Keri N. Althoff, Ph.D., lead author and associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, Baltimore. “This study also demonstrates the importance of using multiple serology platforms, as recommended by the CDC.”
Antibodies are proteins produced in the blood in response to an infection, such as a virus. They play a critical role in fighting infections and are helpful signs that a person may have been exposed to an infection in the past, even if they didn’t show symptoms. In the All of Us study, researchers looked in participant samples for a type of antibodies called IgG. These antibodies do not appear until about two weeks after a person has been infected, indicating that participants with these antibodies were exposed to the virus at least several weeks before their sample was taken. In this study, the first positive samples came from participants in Illinois and Massachusetts on Jan. 7 and 8, 2020, respectively, suggesting that the virus was present in those states in late December.
The study authors noted several limitations to their study. While the study included samples from across the U.S., the number of samples from many states was low. In addition, the authors do not know whether the participants with positive samples became infected during travel or while in their own communities. Ideally, this study could be replicated in other populations with samples collected in the initial months of the U.S. epidemic and with multiple testing platforms to compare results.
All of Us expects to release more information following further analysis, and will offer participants whose samples were included in the study an opportunity to receive their individual results. The presence of antibodies in one’s blood sample does not guarantee that a person is protected from the infection (has immunity), or that any such protection will last.
Deidentified data from the antibody tests will be accessible to researchers for follow-up studies in a future release of the All of Us data analysis platform, the Researcher Workbench, with privacy and security safeguards in place. Currently, the Researcher Workbench includes data from more than 315,000 participants, including information from surveys, electronic health records, wearable devices and more. For full details about data access, visit ResearchAllofUs.org. The study was supported by All of Us and the National Cancer Institute.

A review of more than 9,000 U.S. patients with severe COVID-19 infection showed less than 1% contracted the illness again, with an average reinfection time of 3.5 months after an initial positive test. Those are the findings from a study conducted by researchers from the University of Missouri School of Medicine and MU Health Care.
The researchers teamed up with the MU Institute for Data Science and Informatics and the Tiger Institute for Health Innovation to review data from 62 U.S. health care facilities. They found 63 of the 9,119 patients (0.7%) with severe COVID-19 infection contracted the virus a second time, with a mean reinfection period of 116 days. Of the 63 who were reinfected, two (3.2%) died. Patients categorized as non-white were at greater risk of reinfection than white patients.
“Our analysis also found asthma and nicotine dependence were associated with reinfection,” said lead researcher Adnan I. Qureshi, MD, a professor of clinical neurology at the MU School of Medicine. “However, there was a significantly lower rate of pneumonia, heart failure and acute kidney injury observed with reinfection compared with primary infection.”
Qureshi defined reinfection by two positive tests separated by an interval greater than 90 days after the initial infection resolved, as confirmed by two or more consecutive negative tests. He analyzed data from patients who received serial tests between December 2019 and November 2020.
“This is one of the largest studies of its kind in the U.S., and the important message here is that COVID-19 reinfection after an initial case is possible, and the duration of immunity that an initial infection provides is not completely clear,” Qureshi said.
In addition to Qureshi, the study authors include fellow MU School of Medicine collaborators Iryna Lobanova, MD, research specialist in the Department of Neurology; S. Hasan Naqvi, MD, associate professor of clinical medicine; William Baskett, graduate student; Wei Huang, graduate student; and Chi-Ren Shyu, PhD, Director, MU Institute for Data Science and professor of Informatics, Electrical Engineering and Computer Science.
Their study, “Re-infection with SARS-CoV-2 in Patients Undergoing Serial Laboratory Testing,” was recently published in the journal Clinical Infectious Diseases. Support for this study was provided by the National Institutes of Health. The authors of the study declare that they have no conflicts of interest related to this study and the content does not necessarily represent the official views of the National Institutes of Health.
Story Source:
Materials provided by University of Missouri-Columbia. Note: Content may be edited for style and length.

Changing your eating habits or altering your circadian clock can impact healthy fat tissue throughout your lifespan, according to a preclinical study published today in Nature by researchers with The University of Texas Health Science Center at Houston (UTHealth).
Healthy fat tissue helps provide energy, supports cell growth, protects organs, and keeps the body warm. A good quality diet and one that is consumed in a rhythmic manner (i.e., during our active cycle) is important in maintaining healthy fat, the researchers found.
Adipocyte progenitor cells mature into adipocytes — the healthy fat cells that make up our adipose tissue, which stores energy as fat. Researchers discovered that adipocyte progenitors undergo rhythmic daily proliferation throughout the 24-hour cycle under normal patterns of energy intake.
However, when investigators introduced a high fat diet, or changed the temporal patterns of food consumption so that mice ate equal increments of food during both the sleep and the wake phase, this 24-hour pattern of pre-adipocyte proliferation was destroyed.
“We found that when we fed mice a high-fat diet, it increased the proliferation of preadipocytes and destroyed its rhythmic pattern,” said Kristin Eckel-Mahan, PhD, assistant professor with the Center for Metabolic and Degenerative Diseases at the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases at UTHealth and lead author on the study. “What we project is that over the course of our lifetime, these 24-hour variations in the proliferation of these cells is really important in maintaining healthy fat.”
Throwing off the circadian rhythm and eating a high-fat diet over time will deplete healthy fat cells, and the study suggests that this disruption may be difficult to reverse. Depletion of adipocyte progenitor cells will not allow for healthy new adipocytes to be made within the tissue, ultimately causing defects in fat storage and excess lipid spilling over into other organs, such as the liver and muscle. Eckel-Mahan says having fat in these areas can lead to Type 2 diabetes and insulin resistance.
“In an ideal world, everyone would maintain a normal sleep-wake cycle, and not eat during the wrong hours of the day, so not too late before bed or into the early morning. You should also steer away from high-fat diets, which we have now shown destroys the rhythmic proliferation of our preadipocytes. The 24-hour clock we have is important when it comes to our healthy fat, and we need to protect it as much as we can,” said first author Aleix Ribas-Latre, PhD, with the Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig in Germany.
Story Source:
Materials provided by University of Texas Health Science Center at Houston. Original written by Jeannette Sanchez. Note: Content may be edited for style and length.

A new model that applies artificial intelligence to carbohydrates improves the understanding of the infection process and could help predict which viruses are likely to spread from animals to humans. This is reported in a recent study led by researchers at the University of Gothenburg.
Carbohydrates participate in nearly all biological processes — yet they are still not well understood. Referred to as glycans, these carbohydrates are crucial to making our body work the way it is supposed to. However, with a frightening frequency, they are also involved when our body does not work as intended. Nearly all viruses use glycans as their first contact with our cells in the process of infection, including our current menace SARS-CoV-2, causing the COVID-19 pandemic.
A research group led by Daniel Bojar, assistant professor at the University of Gothenburg, has now developed an artificial intelligence-based model to analyze glycans with an unprecedented level of accuracy. The model improves the understanding of the infection process by making it possible to predict new virus-glycan interactions, for example between glycans and influenza viruses or rotaviruses: a common cause for viral infections in infants.
As a result, the model can also lead to a better understanding of zoonotic diseases, where viruses spread from animals to humans.
“With the emergence of SARS-CoV-2, we have seen the potentially devastating consequences of viruses jumping from animals to humans. Our model can now be used to predict which viruses are particularly close to “jumping over.” We can analyze this by seeing how many mutations would be necessary for the viruses to recognize human glycans, which increases the risk of human infection. Also, the model helps us predict which parts of the human body are likely targeted by a potentially zoonotic virus, such as the respiratory system or the gastrointestinal tract,” says Daniel Bojar, who is the main author of the study.
In addition, the research group hopes to leverage the improved understanding of the infection process to prevent viral infection. The aim is to use the model to develop glycan-based antivirals, medicines that suppress the ability of viruses to replicate.
“Predicting virus-glycan interactions means we can now search for glycans that bind viruses better than our own glycans do, and use these “decoy” glycans as antivirals to prevent viral infection. However, further advances in glycan manufacturing are necessary, as potential antiviral glycans might include diverse sequences that are currently difficult to produce,” Daniel Bojar says.
He hopes the model will constitute a step towards including glycans in approaches to prevent and combat future pandemics, as they are currently neglected in favor of molecules that are simpler to analyze, such as DNA.
“The work of many groups in recent years has really revolutionized glycobiology and I think we are finally at the cusp of using these complex biomolecules for medical purposes. Exciting times are ahead,” says Daniel Bojar.
Story Source:
Materials provided by University of Gothenburg. Original written by Ulrika Ernström. Note: Content may be edited for style and length.

On the outside, animals often appear bilaterally symmetrical with mirror-image left and right features. However, this balance is not always reflected internally, as several organs such as the lungs and intestines are left-right (LR) asymmetrical. Researchers at Osaka University, using an innovative technique for imaging movement of cell nuclei in living tissue, have determined the patterns of nuclear alignment responsible for LR-asymmetrical shaping of internal organs in the developing embryo.
Embryogenesis involves complex genetic and molecular processes that transform a single-celled zygote into a complete, living individual with multiple functional axes, including the LR axis. A long-standing conundrum of Developmental Biology is the breaking of LR symmetry in the developing embryo to initiate lateralization (dominance of one side over the other) of organs and other structures of the body along the LR axis. Mechanisms that induce LR asymmetry are well known in vertebrates; however, the biomechanics in invertebrates remain uncertain.
The research team focused on the development of the intestine, in particular the anterior midgut (AMG) of the Drosophila (fruit fly) as an appropriate model to study LR-asymmetric development in invertebrates. “Proper organ development often requires nuclei to move to a specific position within the cell,” first author Dongsun Shin explains. “Our previous studies had revealed the molecular signaling pathways as well as the proteins responsible for the biomechanical control of asymmetric development, but the dynamics had not yet been determined.”
To meet the challenge of dynamically tracking nuclei in living tissue, the researchers innovated a new method to investigate nuclear migration. Using a confocal laser scanning microscope, they obtained three-dimensional (3D) time lapse videos of immunostained Drosophila midgut at the appropriate embryonal stage. Then, applying mathematical modeling and computational imaging techniques they generated 3D-surface animated models of nuclear migration in the visceral muscles.
Through 3-D time-lapse movies, the researchers identified the initial LR-symmetrical distribution of AMG muscle nuclei along the antero-posterior (front-to-back) axis — termed ‘proper nuclear positioning.’ Further, they vividly imaged ‘collective nuclear behavior’ in which crowded nuclei actively rearranged their relative positions with LR symmetry. This symmetric initial ‘proper nuclear positioning’ and ‘collective nuclear behavior’ are responsible for subsequent LR-asymmetric development of the AMG. In contrast, experiments in genetically modified Drosophila embryos demonstrated that when the nuclei aligned with LR-asymmetry, the subsequent LR-asymmetric development of the AMG was lost. It is known that nuclei are the toughest intracellular organelles. Thus, based on these results, the researchers speculated that nuclei may act like structural pillars if they are collectively aligned, which support the structure of the gut and influence LR-asymmetrical changes in shape during its development.
Senior author Kenji Matsuno explains the potential of their findings: “This new method of tracking moving nuclei in vital tissue has helped clarify the role of nuclear alignment in asymmetrical shaping of internal organs during normal development. In addition, our findings are expected to be applied to controlling the shape of regenerative organs. This knowledge could potentially shape future research into organ regeneration which may have applications such as growing artificial organs to model disease mechanisms.”
Story Source:
Materials provided by Osaka University. Note: Content may be edited for style and length.

SharecloseShare pageCopy linkAbout sharingimage copyrightGetty ImagesThe number of Americans who have died from Covid-19 has surpassed 600,000 – the most of any nation – according to data from John Hopkins University.The US also ranks highest in total number of recorded cases, with nearly 33.5 million infections since 2020.This latest milestone comes as President Joe Biden’s goal of getting 70% of US adults vaccinated by 4 July appears increasingly likely to fail.Over 173 million people, around 52% of the US, have had at least one dose.Roughly 43% of the US population, or about 144 million Americans, are fully vaccinated, according to the Centers for Disease Control and Prevention (CDC). The CDC says people are fully vaccinated at least two weeks after their final vaccine dose.As of Tuesday, 600,012 people in the US have died of complications brought on by the coronavirus.Brazil and India have reported the next highest death tolls, with Brazil at more than 488,000 deaths and India at more than 377,000.It took around four months for the US to go from 500,000 to 600,000 deaths – about as long as it took to go from none to 100,000. It marks a significant change from the height of the pandemic when the death toll jumped from 300,000 to 400,000 in one month last winter.But the country’s vaccination rate has begun to fall to around one million doses administered per day – down from a high this April of nearly 3.4 million after it was first made available to all adults over 18.Though a majority of adult Americans have received at least one dose, the percentages vary wildly from state to state. Vermont has fully vaccinated 71% of its residents, but only 36% of Mississippians have received both jabs, according to a New York Times database.Health experts have warned of vaccine scepticism and misinformation. A recent Kaiser Family Foundation poll found around a third of US adults were not planning on getting vaccinated yet.The vaccination hesitancy has led to measures like lotteries and giveaways in states eager to get people signed up for jabs.Ohio has been selecting one vaccinated resident each week to win $1m (£708,000). On Tuesday, California will give $1.5m each to 10 residents. Other winnable items include alcohol, cannabis, guns, food vouchers and gift cards.The White House is also working to boost vaccinations. As part of a national tour to raise awareness, Vice-President Kamala Harris travelled to South Carolina – a state with a relatively low vaccination rate – to visit a pop-up medical clinic on Monday.”They are safe. And they are free. And they are effective. And it is that simple,” Ms Harris said during her visit. On Monday night, the governor of California – the most populous US state – announced a “grand reopening”.The state, which ordered the first coronavirus lockdown, will now allow vaccinated people to not wear masks or socially distance in most settings. Public health measures remain for events with over 5,000 people.Also on Monday, US drug maker Novavax announced that its vaccine was found to be 90.4% effective after testing was conducted on 30,000 participants.The company said they plan to file for US federal approval in the third business quarter. If approved, it will be the fourth coronavirus vaccine to hit the US market.G7 leaders promise one billion vaccine dosesHow many vaccines are rich countries sharing?The Biden administration has already ordered enough doses of the existing vaccines for the entire US population, US media report, so Novavax may become part of the global vaccine-sharing deal to donate doses.The US has already pledged over half a billion doses of the Pfizer vaccine to the scheme.