Categories : NeurologyTags :

Study Resolves Long-standing Question on Gating of Ion Channels

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Ion channels play a crucial role in many cellular processes, including neuronal communication, muscle contraction or cell proliferation. Most multi subunit ion channels exist in two functional states, either closed or open. During gating, one should expect that all subunits undergo conformational changes – but there are no intermediate conduction levels. To find out why, researchers from the University of Vienna and the Washington University in St. Louis created a smart model system. The study is currently published in Nature Communications.

Ion channels are membrane proteins that regulate the electrical activity of cells. In this study the scientific team investigated the inwardly rectifying potassium channel Kir2. This channel is crucial for maintaining a negative membrane potential in many cells. These channels are promising drug targets for treatment of cardiovascular diseases. To foster drug development, a detailed understanding of the gating mechanism is important.

Intelligent model system & innovative methods

“We designed a model system that allowed us to visualise the gating of individual subunits and track conductance changes,” explains Grigory Maksaev from the Washington University in St. Louis. As a model system, the inwardly rectifying potassium channel Kir2 was used. This channel is crucial for maintaining a negative membrane potential in many cells. “We introduced an acidic residue near the channel gate. This led to novel states, so-called sub-conductance states” explains Eva Plessl from the Department of Pharmaceutical Sciences, University of Vienna. The life times of these sub-states were long enough to resolve them experimentally. Each of the observed sub-states represents a distinct subunit conformation. Interestingly, the sub-state occupancy is titratable by pH. “This suggests that protonation or deprotonation of individual acidic residues causes this phenomenon,” explains Sun-Joo Lee from the Washington University in St. Louis.

Sour is…less conductive

“Molecular dynamics simulations with different protonation states of the acidic residue support this finding,” explains Anna Weinzinger from the Department of Pharmaceutical Sciences, University of Vienna. The study reveals that each subunit gating transition leads to conductance level changes. This suggests that for a fully open channel, all subunits must move together. “By designing a smart model system, we have answered a long-standing question about ion channel gating,” explains Colin Nichols from the Washington University in St. Louis.

Source: University of Vienna

Categories : Injury & TraumaTags :

Texting While Walking Increases the Risk of Slipping and Falling

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People are increasingly glued to their smartphones, texting even as they walk, which has inspired a wide range of studies: some have shown that they can multitask and navigate around obstacles while other have shown that they are more likely to walk into traffic. But how likely are they to avoid a fall if they slip? University of New South Wales (UNSW) researchers investigated this by simulating an environment with random slipping threats, and reported in the journal Heliyon that texting increases the risk of falling in response to walkway hazards.

“On any day it seems as many as 80% of people, both younger and older, may be head down and texting. I wondered: is this safe?” says senior author Matthew A. Brodie, a neuroscientist and engineer at the UNSW Graduate School of Biomedical Engineering. “This has made me want to investigate the dangers of texting while walking. I wanted to know if these dangers are real or imagined and to measure the risk in a repeatable way.”

The team recruited 50 UNSW undergraduate students from his “Mechanics of the Human Body” course for this experiment. Brodie and co-author Yoshiro Okubo invented a tiled hazard walkway at Neuroscience Research Australia’s gait laboratory, which halfway through had a tile that could be adjusted to slide out of place and cause a person stepping on it to slip. Students wore a safety harness and sensors that collected their motion data. They then were asked to go along the walkway either without texting or while typing “The quick brown fox jumps over the lazy dog.”

To better simulate the uncertainty of real life, students were only told that they may or may not slip. This allowed the researchers to study how texting pedestrians might anticipate and try to prevent a potential slip, such as by leaning forward.

“What surprised me is how differently people responded to the threat of slipping,” says Brodie. “Some slowed down and took a more cautious approach. Others sped up in anticipation of slipping. Such different approaches reinforce how no two people are the same, and to better prevent accidents from texting while walking, multiple strategies may be needed.”

Despite motion data showing that texting participants tried to be more cautious in response to a threat, this did not counteract their risk of falling. When participants went from leaning forwards (such as over a phone) to slipping backwards, their motion sensors showed an increase in the range of their ‘trunk angle’. Researchers used this number to measure whether the texting condition was making students more likely to fall, and they found that the average trunk angle range during a fall significantly increased if a student was texting.

Walking also caused the texters’ accuracy to decrease. The highest texting accuracy occurred when participants were seated, but accuracy decreased even as walking participants were cautioned about a potential slip that did not occur. The lowest accuracy, however, occurred in conditions where participants did slip.

The researchers note that young people may be more likely to take risks even if they are aware that texting and walking could increase their likelihood of falling. For that reason, the authors suggest that educational initiatives such as signs might be less effective in reaching this population. In addition to education, the researchers also suggest that phones could implement locking technology similar to what is used when users are driving. The technology could detect walking activity and activate a screen lock to prevent texting during that time. In future research, the team plans on looking into the effectiveness of this intervention.

Source: Science Daily

Categories : Antibiotics GeneticsTags :

Genetic Mechanism Increases Resistance to the Antibiotic Albicidin by 1000-fold

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A new analysis shows that infectious bacteria exposed to the promising antibiotic albicidin rapidly develop up to a 1000-fold increase in resistance via a gene amplification mechanism. Mareike Saathoff of Freie Universität Berlin, Germany, and colleagues presented these findings in the open access journal PLOS Biology.

Bacterial resistance to antibiotics is a growing problem associated with millions of deaths around the world every year. Understanding how bacteria evolve resistance is key to developing more effective antibiotics and strategies for using them.

In recent years, albicidin has emerged as a promising antibiotic capable of killing a wide range of bacterial species by disrupting their DNA replication. Researchers are working to develop new albicidin-based medications; yet, despite its promise, some bacteria are able to develop resistance to albicidin.

To further investigate albicidin resistance mechanisms, Saathoff and colleagues conducted a suite of experiments employing a broad set of tools, including RNA sequencing, protein analysis, X-ray crystallography, and molecular modeling. They found that two bacteria often associated with human infection, Salmonella typhimurium and Escherichia coli, develop resistance to albicidin when exposed to increasingly higher concentrations of the compound. Their analysis narrowed down the source of this resistance to an increase in the number of copies of a gene known as STM3175 (YgiV) in the bacterial cells, which is amplified in each new generation of cells as they multiply. STM3175 encodes a protein that interacts with albicidin in such a way that protects the bacteria from it.

Further experiments showed that the same albicidin-resistance mechanism is widespread among both pathogenic and harmless bacteria, including the microbes Vibrio vulnificus, which can infect wounds, and Pseudomonas aeruginosa, which can cause pneumonia and other infections. These findings could help inform the ongoing development of albicidin-based antibiotic strategies.

The authors add, “Our study reveals a gene duplication and amplification-based mechanism of a transcriptional regulator in Gram-negative bacteria, that mediates resistance to the peptide antibiotic albicidin.”

Source: Science Daily

Categories : COVID HospitalsTags :

Nose-picking Healthcare Workers Were More Likely to Get COVID

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A study of healthcare workers (HCW) found that those who picked their nose were more likely to get COVID than the people who refrained from such explorations. The Dutch researchers published their probing results in the journal PLOS One.

In the early stages of the COVID pandemic, researchers noted a wide range of efforts to prevent the spread of SARS-CoV-2, such as the wearing of personal protective equipment and maintaining social distancing, especially in the hospital setting. Much research went into the impacts of, eg, wearing glasses on the effectiveness of masking, but little if any attention was paid to a widespread but secretive habit.

Sikkens and colleagues retrospectively surveyed healthcare workers at Amsterdam University Medical Centers were in December 2021 about their behaviours during the first and second waves of the pandemic. They matched these responses were matched against prospectively collected COVID test results at the hospitals from March to October 2020. The nose pickers were nearly three times more likely to catch COVID (17.3% vs 5.9%) than those who refrained at all costs. Surprising results were found for those HCWs who owned up to the habit.

Secret nose pickers can take some comfort in that 85% of the cohort admitted that they picked their nose either daily, weekly, or monthly, and nose pickers tended to be younger. More men picked their nose (90%) than women (83%), and doctors were the most likely to be among the nose-picking offenders: 100% of residents admitted to it, along with 91% of specialists.

Sikkens et al. noted that one limitation of the study was that nose pickers were not asked about “the depth of penetration and eating of boogers”.

Other behaviours such nail biting, having a beard were not associated with COVID infection, nor was wearing glasses, though it showed a relevant trend. Interestingly, nose picking frequency was not linked to difference in COVID infection risk; 27% of those who reported monthly picking, 35% among weekly pickers, and 32% of daily pickers.

Frequency of nose picking did not appear to be linked with any difference in COVID infection risk, with positive cases in 27% of those who reported monthly picking, 35% among weekly pickers, and 32% of daily pickers. No participants reported picking their nose every hour, thankfully.

One-third of the cohort reported nail biting, two-thirds wore glasses, and 31% of the men had beards.

A study strength was that SARS-CoV-2 positivity was determined by prospective longitudinal serological sampling, though this may not be generalisable to the current era of vaccines and circulating Omicron variants. The retrospective nature of the survey may have introduced recall bias.

Sikken et al. noted that it is surprising that SARS-CoV-2 transmission routes had been so thoroughly researched, yet simple behaviours had been overlooked. “Possibly this sensitive subject is still taboo in the health care profession. It is commendable we assume HCWs to not portray bad habits, yet we too are only human after all, as illustrated by the pivotal proportion of nose pickers in our cohort (84.5%).”

Categories : Diseases, Syndromes and ConditionsTags :

Inflammation Impedes the Development of Malaria Parasites

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Researchers have found that inflammation can slow down the development of malaria parasites in the bloodstream, which may lead to a new strategy for preventing or limiting severe disease.

The malaria-causing Plasmodium parasites invade and multiply within red blood cells. Studies have shown that the parasites can rapidly sense and respond to conditions within the host by intimately syncing with their internal body clocks. While it is known that the body’s nutrient levels and daily circadian rhythms affect the parasites’ development, little was known about the impact of host inflammation on the parasites.

This animal-model study, led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and the Kirby Institute and published in the journal mBio, reveals that when the body’s immune system responds to inflammation it alters the plasma’s chemical composition, directly impeding the maturation of the Plasmodium parasites in the bloodstream.

University of Melbourne’s Associate Professor Ashraful Haque, a senior author of the paper, said this work highlights the captivating dynamic of the host-parasite relationship.

“First, we discovered that inflammation in the body prevented the early stage of the parasites from maturing. We also noticed that inflammation triggered significant changes in the composition of the plasma – we were actually quite surprised by the magnitude of these changes,” said Associate Professor Haque.

“As we dug deeper, we found substances in the altered plasma that, we believe, are what may inhibit parasite growth in the body. This work reveals a new mechanism that slows down the malaria parasite’s development in the bloodstream. Our research was done using animal models, so it would be really interesting to study if such inhibitory mechanisms occur in humans too.”

Dr David Khoury, co-senior author of the paper, said the scientists found a remarkable response by the parasites to the changes in their environment.

“Parasites residing in red blood cells rapidly sense and respond to their new environment, showing fascinating adaptability. Using cutting-edge genome sequencing technology, we observed that even after just four hours in this changed plasma, the parasites adjusted their genetic and protein activity, resulting in slower maturation within red blood cells. It’s almost like the parasites actively sense an inhospitable host environment, and as a result trigger a coping mechanism,” said Dr Khoury.

“We believe this is the first study to show that inflammation can change how individual parasites behave genetically in the body.”

Professor Miles Davenport, co-senior author of the paper, said this work on the interaction between systemic host inflammation and malaria parasite maturation offers several potential benefits.

“This study, while based on animal models, broadens our understanding of malaria. It provides a foundation for further investigations into the specific mechanisms involved in the modulation of parasite maturation by inflammation, and opens avenues for future studies to explore the identified inhibitory factors, genetic changes and their implications for malaria development,” said Professor Davenport.

Source: The Peter Doherty Institute for Infection and Immunity

Categories : Cancer Diet and NutritionTags :

Study Shows a Link Between Sugar-sweetened Beverages and Liver Cancer

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One of the first studies to look at the association between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality, has found an 85% increase in liver cancer incidence between postmenopausal women who consume one sweetened drink per day and those who consume them rarely. Results from the study, which was led by Brigham and Women’s Hospital, are published in JAMA.

“To our knowledge, this is the first study to report an association between sugar sweetened beverage intake and chronic liver disease mortality,” said first author Longgang Zhao, PhD, of the Brigham’s Channing Division of Network Medicine. Zhao is a postdoctoral researcher who works with senior author Xuehong Zhang, MBBS, ScD, in the Channing Division. “Our findings, if confirmed, may pave the way to a public health strategy to reduce risk of liver disease based on data from a large and geographically diverse cohort.”

This observational study included nearly 100 000 postmenopausal women from the large, prospective Women’s Health Initiative study. Participants reported their usual soft drink, fruit drink (not including fruit juice) consumption, and then reported artificially sweetened beverage consumption after three years. Participants were followed for a median of more than 20 years. Researchers looked at self-reported liver cancer incidence and death due to chronic liver disease such as fibrosis, cirrhosis, or chronic hepatitis, which were further verified by medical records or the National Death Index.

A total of 98 786 postmenopausal women were included in the final analyses. The 6.8% of women who consumed one or more sugar-sweetened beverages daily had an 85% higher risk of liver cancer and 68% higher risk of chronic liver disease mortality compared to those who had fewer than three sugar sweetened beverages per month. No such increase was observed for consumption of artificially-sweetened beverages.

The authors note that the study was observational, and causality cannot be inferred, and relied on self-reported responses about intake, sugar content and outcomes. More studies are needed to validate this risk association and determine why the sugary drinks appeared to increase risk of liver cancer and disease. Furthermore, more research is needed to elucidate the potential mechanisms by integrating genetics, preclinical and experimental studies, and -omics data.

Source: Mass General Brigham

Categories : Gastrointestinal NeurologyTags :

Possible Dementia Risk from Long Term Proton Pump Inhibitor Use

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People who take proton pump inhibitors for acid reflux four-and-a-half years or more may have a higher risk of dementia compared to people who do not take these medications, according to new research published in Neurology.

Acid reflux is when stomach acid flows into the oesophagus, usually after a meal or when lying down, resulting in heartburn and ulcers. People with frequent acid reflux may develop gastroesophageal reflux disease, or GERD, which can lead to cancer of the oesophagus. Proton pump inhibitors reduce stomach acid by targeting the enzymes in the stomach lining that produce that acid.

“Proton pump inhibitors are a useful tool to help control acid reflux, however long-term use has been linked in previous studies to a higher risk of stroke, bone fractures and chronic kidney disease,” said study author Kamakshi Lakshminarayan, MBBS, PhD, of the University of Minnesota School of Public Health in Minneapolis, and a member of the American Academy of Neurology. “Still, some people take these drugs regularly, so we examined if they are linked to a higher risk of dementia. While we did not find a link with short-term use, we did find a higher risk of dementia associated with long-term use of these drugs.”

The study included 5712 people, aged 45 and up, without dementia at the start of the study. They had an average age of 75.

Researchers determined if participants took acid reflux drugs by reviewing their medications during study visits and during yearly phone calls. Of the participants, 1490 people, or 26%, had taken the drugs. Participants were then divided into four groups based on whether they had taken the drugs and for how long, as follows: people who did not take the drugs; those who took the drugs for up to 2.8 years; those who took them for 2.8 to 4.4 years; and people who took them for more than 4.4 years.

Participants were then followed for a median duration of 5.5 years. During this time, 585 people, or 10%, developed dementia.

Of the 4222 people who did not take the drugs, 415 people developed dementia, or 19 cases per 1000 person-years. Person-years represent both the number of people in the study and the amount of time each person spends in the study. Of the 497 people who took the drugs for more than 4.4 years, 58 people developed dementia, or 24 cases per 1000 person-years.

After adjusting for factors such as age, sex and race, as well as health-related factors such as high blood pressure and diabetes, researchers found people who had been taking acid reflux drugs for more than 4.4 years had a 33% higher risk of developing dementia than people who never took the drugs.

Researchers did not find a higher risk of dementia for people who took the drugs for fewer than 4.4 years.

“More research is needed to confirm our findings and explore reasons for the possible link between long-term proton pump inhibitor use and a higher risk of dementia,” said Lakshminarayan. “While there are various ways to treat acid reflux, such as taking antacids, maintaining a healthy weight, and avoiding late meals and certain foods, different approaches may not work for everyone. It is important that people taking these medications speak with their doctor before making any changes, to discuss the best treatment for them, and because stopping these drugs abruptly may result in worse symptoms.”

A limitation of the study was that participants were asked once a year about medication use, so researchers estimated use between annual check-ins. If participants stopped and restarted acid reflux drugs in between check-ins, estimation of their use may have been inaccurate. The authors were also unable to assess if participants took over the counter acid reflux drugs.

Source: American Academy of Neurology

Categories : Environmental Effects Surgeries & ProceduresTags :

Surgeons Find Microplastics in Heart Tissue During Surgery

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Microplastics seem ubiquitous in today’s environment, being found everywhere from rivers to inside the stomach. Now, in a pilot study of patients who underwent heart surgery, researchers in ACS’ Environmental Science & Technology report that they have found microplastics in many heart tissues. They also report evidence suggesting that microplastics were unexpectedly introduced during the procedures.

Microplastics are plastic fragments less than 5mm wide, or about the size of a pencil eraser. Research has shown that they can enter the human body through the mouth, nose and other body cavities with connections to the outside world. Yet many organs and tissues are fully enclosed inside a person’s body, and scientists lack information on their potential exposure to, and effects from, microplastics. So, Kun Hua, Xiubin Yang and colleagues wanted to investigate whether these particles have entered people’s cardiovascular systems through indirect and direct exposures.

In a pilot experiment, the researchers collected heart tissue samples from 15 people during cardiac surgeries, as well as pre- and post-operation blood specimens from half of the participants. Then the team analysed the samples with laser direct infrared imaging and identified 20 to 500 micrometre-wide particles made from eight types of plastic, including polyethylene terephthalate, polyvinyl chloride and poly(methyl methacrylate). This technique detected tens to thousands of individual microplastic pieces in most tissue samples, though the amounts and materials varied between participants. The blood samples also all contained plastic particles, but after surgery their average size decreased, and the particles came from a wider range of plastics.

Although the study had a small number of participants, the researchers say they have provided preliminary evidence that various microplastics can accumulate and persist in the heart and its innermost tissues. They add that the findings show how invasive medical procedures are an overlooked route of microplastics exposure, providing direct access to the bloodstream and internal tissues. More studies are needed to fully understand the effects of microplastics on a person’s cardiovascular system and their prognosis after heart surgery, the researchers conclude.

Source: American Chemical Society

Categories : Neurodegenerative DiseasesTags :

Non-invasive Transcranial Stimulation Improves Walking in Parkinson’s Disease

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Altered gait is common in patients with Parkinson’s disease (PD), and the usefulness of treatments is limited. Researchers in Japan have developed a novel transcranial stimulation method using external electrodes, the team demonstrated significant gait improvements in PD patients. The results, which also showed improvements for other neurological disorders, are published in the Journal of Neurology, Neurosurgery & Psychiatry.

Motor function declines characterises PD, particularly in relation to gait disorders, manifesting as decreased step length, reduced arm swing, slow movements, rigidity, and postural instability, which are prevalent among patients with PD. While non-pharmacological approaches like transcranial direct current stimulation show promise in improving motor function, recent research focuses on gait-combined closed-loop stimulation, which synchronises brain stimulation with the individual’s gait rhythm.  proposes a novel intervention for gait improvement, thus creating new hope for patients with PD.

“We recently developed a novel neuromodulation approach using gait-combined closed-loop transcranial electrical stimulation (tES) and demonstrated promising gait improvements in patients who are post-stroke. Here, we tested the efficacy of this intervention in patients with Parkinsonian gait disturbances,” explains lead author Ippei Nojima from Shinshu University and Nagoya City University, Japan.

To this end, the clinical researchers from Japan recruited 23 patients with PD or Parkinson’s syndrome. All study participants were randomly assigned to receive either the active treatment or sham treatment.

During the course of the trial, a low-current electrode (up to 2mA) was externally affixed to the occipital region of the head. A reference electrode was then placed in the neck region to establish a stable electrical reference point and to complete the electrical circuit. The treatment included performing tES on the cerebellum in a non-invasive manner. The brain side showing severe impact was specifically targeted during the electrotherapy.

“Gait disturbance lowers activities of daily living in patients with PD and related disorders. However, the effectiveness of pharmacological, surgical, and rehabilitative treatments is limited. Our novel intervention might be able to improve physical function for not just patients with PD but also for those with other disabilities,” comments senior author Yoshino Ueki from the Department of Rehabilitation Medicine at Nagoya City University.

The cerebellum plays a key role in gate control, so electrical stimulation of this region is likely to exert therapeutic benefits. The therapy showed encouraging results after just ten repetitions. The treatment group showed a significant improvement in gait parameters including speed, gait symmetry, and stride length.

Professor Nojima said, “These findings showed that gait-combined closed-loop tES over the cerebellum improved Parkinsonian gait disturbances, possibly through the modulation of brain networks generating gait rhythms.”

Interestingly, no patient dropped out during the study. Moreover, patients from both the groups (treatment and sham) showed good and comparable compliance. Side effects such as skin irritation, vertigo, or odd sensations/perceptions were also not observed in any of the volunteering patients. This study has special significance, considering the fact that Japan is witnessing a sharp rise in its elderly population.

Source: Shinshu University

Categories : Cardiovascular Disease ExerciseTags :

Health Benefits Appear Even with Fewer Steps per Day

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Contrary to previous belief, fewer numbers of daily steps are necessary for health benefits to appear, according to the largest analysis to investigate this. The study, published in the European Journal of Preventive Cardiology, found that walking at least 3967 steps a day started to reduce the risk of dying from any cause, and 2337 steps a day reduced the risk of dying from cardiovascular disease.

The new analysis included 226 889 people from 17 different studies around the world. It showed that the risk of dying from any cause or from cardiovascular disease decreases significantly with every 500 to 1000 extra steps you walk. An increase of 1000 steps a day was associated with a 15% reduction in the risk of dying from any cause, and an increase of 500 steps a day was associated with a 7% reduction in dying from cardiovascular disease.

The researchers, led by Maciej Banach, Professor of Cardiology at the Medical University of Lodz, Poland, and Adjunct Professor at the Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, found that even if people walked as many as 20 000 steps a day, the health benefits continued to increase, with no upper limit found yet.

“Our study confirms that the more you walk, the better,” says Prof Banach. “We found that this applied to both men and women, irrespective of age, and irrespective of whether you live in a temperate, sub-tropical or sub-polar region of the world, or a region with a mixture of climates. In addition, our analysis indicates that as little as 4000 steps a day are needed to significantly reduce deaths from any cause, and even fewer to reduce deaths from cardiovascular disease.”

According to World Health Organization data, insufficient physical activity is the fourth most frequent cause of death in the world, with 3.2 million deaths a year related to physical inactivity. The COVID-19 pandemic also resulted in a reduction in physical activity, and activity levels have not recovered two years on from it.

Dr Ibadete Bytyçi from the University Clinical Centre of Kosovo, Pristina, Kosovo, senior author of the paper, says: “Until now, it’s not been clear what is the optimal number of steps, both in terms of the cut-off points over which we can start to see health benefits, and the upper limit, if any, and the role this plays in people’s health. However, I should emphasise that there were limited data available on step counts up to 20 000 a day, and so these results need to be confirmed in larger groups of people.”

This meta-analysis is the first not only to assess the effect of walking up to 20 000 steps a day, but also to look at whether there are any differences depending on age, sex or where in the world people live.

The studies analysed by the researchers followed up participants for a median (average) of seven years. The mean (average) age was 64, and 49% of participants were female.

In people aged 60 years or older, the size of the reduction in risk of death was smaller than that seen in people aged younger than 60 years. In the older adults, there was a 42% reduction in risk seen in those who walked 6000–10 000 steps a day, while there was a 49% reduction in risk in younger adults who walked 7000–13 000 steps a day.

Prof Banach says: “In a world where we have more and more advanced drugs to target specific conditions such as cardiovascular disease, I believe we should always emphasise that lifestyle changes, including diet and exercise, which was a main hero of our analysis, might be at least as, or even more effective in reducing cardiovascular risk and prolonging lives. We still need good studies to investigate whether these benefits may exist for intensive types of exertion, such as marathon running and iron man challenges, and in different populations of different ages, and with different associated health problems. However, it seems that, as with pharmacological treatments, we should always think about personalising lifestyle changes.”

Strengths of the meta-analysis include its size and that it was not restricted to looking at studies limited to a maximum of 16 000 steps a day. Limitations include the observational nature of the study. The impact of step counts was not tested on people with different diseases; all the participants were generally healthy when they entered the studies analysed. The researchers were not able to account for differences in race and socioeconomic status, and the methods for counting steps were not identical in all the studies included in this meta-analysis.

Source: European Society of Cardiology