Tag: 30/4/21

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Common Probiotic Altered to Grow in Dairy Products

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A glass of milk. Source: Pixabay via Pexels

Researchers at the University of Helsinki have created a strain of the Lacticaseibacillus rhamnosus GG probiotic that can reproduce in dairy products.

Lacticaseibacillus rhamnosus GG, or LGG, is the most studied probiotic bacterium in the world. However, it cannot utilise lactose found in milk or break down the milk protein casein. This makes the bacterium grow poorly in milk and is the reason why it must be added separately to probiotic dairy products.

While attempts have been made to get L. rhamnosus GG to thrive in milk through genetic engineering, strict restrictions have prevented the use of such modified bacteria in human food.

Thanks to a recent breakthrough made at the University of Helsinki, Finland, with researchers from the National Institute for Biotechnology and Genetic Engineering, Pakistan, features have now been successfully added to the LGG probiotic without gene editing, making it able to grow in milk.

The method instead took advantage of conjugation, a DNA exchange technique used in certain bacterial groups to transfer their traits to other bacteria. A bacterium produces a copy of its plasmid, a ring-shaped piece of DNA, and then transfers it to an adjacent bacterium. The spread of plasmids, which carry traits useful for bacteria, can be rapid among bacterial communities – and can also further the spread of problematic traits such as antibiotic resistance.

A specific Lactococcus lactis bacterial strain grown in the same place provided the lactose and casein-utilising plasmid to the Lacticaseibacillus rhamnosus GG.

“The new LGG strain is not genetically modified, which makes it possible to consume it and any products containing it without any permit procedures,” explained project leader Per Sari, Professor of Microbiology at the University of Helsinki.

The new strain can be used as a starting point in the development of new dairy products where the probiotic concentration increases already in the production stage. In other words, the probiotic need not be separately added to the final product. Furthermore, lactose- and casein-hydrolysing bacteria added to milk could help produce products suitable for people with dairy allergies.

This new LGG strain could also be better suited to growing in the infant gut, where it can utilise the casein and lactose in breastmilk to grow, thereby producing more protective lactic acid than the original strain.

“Lactic acid lowers the pH of the surface of the intestine, reducing the viability of many gram-negative pathogenic bacteria, such as E. coli, Salmonella and Shigella, which threaten the health of infants. Moreover, in larger numbers the new LGG strain can potentially be more effective at protecting infants than the old strain. After all, LGG has previously been shown to alleviate infantile atopic dermatitis and boost the recovery of the gut microbiota after antibiotic therapies.”

The researchers are in discussions about further applications of their research.

Source: News-Medical-Net

Journal information: Hussain, N., et al. (2021) Generation of Lactose- and Protease-Positive Probiotic Lacticaseibacillus rhamnosus GG by Conjugation with Lactococcus lactis NCDO 712. Applied and Environmental Microbiology. doi.org/10.1128/AEM.02957-20.

Categories : Cardiovascular DiseaseTags : Leave a comment

Blood Pressure Meds May Lower Heart Risk Even For the Healthy

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Red blood cells. CC0 Commons


Blood pressure-lowering medication can prevent serious cardiovascular conditions such as strokes, heart failure and heart attacks even in adults with normal blood pressure, according to new research published in The Lancet.

Importantly, the study found the beneficial effects of treatment were similar regardless of the starting blood pressure level, in both people who had previously had a heart attack or stroke and in those who had never had heart disease.

The authors say that the findings have immediate and important implications for global clinical guidelines that typically limit blood pressure-lowering treatment to individuals with high blood pressure (typically above 140/90 mmHg).

“Our findings are of great importance to the debate concerning blood pressure treatment,” said lead author Professor Kazem Rahimi at the University of Oxford. “This new and best available evidence tells us that decisions to prescribe blood pressure medication should not be based simply on a prior diagnosis of cardiovascular disease or an individual’s blood pressure level. Instead, medication should be viewed as an effective tool for preventing cardiovascular disease in people at increased risk of developing heart disease or stroke. Clinical guidelines should be changed to reflect these findings.”

He cautioned, “We’re not saying that everyone must begin treatment. The decision will depend on an individual’s risk factors for developing cardiovascular disease, the potential for side effects and patient choice.”

In many Western countries as well as developing economies like South Africa, heart disease and stroke, linked to high blood pressure, are among the leading causes of death. Blood pressure medication is widely acknowledged as protecting people with a history of heart attack or stroke from having a recurrence, but there is debate about their use in people with normal or mildly elevated blood pressure.

To date, conflicting findings have come from studies examining whether blood pressure-lowering medication is equally beneficial in people with and without a history of cardiovascular disease, and at lower blood pressures warranting treatment (typically considered 140/90 mmHg or higher). This has led to contradictory treatment recommendations around the world.

For the current analysis, the Blood Pressure Lowering Treatment Triallists’ Collaboration pooled data from 344 716 adults in 48 randomised trials to investigate the effects of blood pressure-lowering medications.

Participants were classified as those with a prior diagnosis of cardiovascular disease (157 728 participants – secondary prevention group) and those without (186,988 – primary prevention group, without cardiovascular disease).

Each group was then divided into seven subgroups based on levels of systolic blood pressure at the start of the study. About 20% (31 239) of participants with prior cardiovascular disease and 8% (14 928) of those who had never had cardiovascular disease had normal or high-normal systolic blood pressure at the start of the trials (systolic blood pressure less than 130 mmHg).

Over an average of four years follow-up, 4324 participants experienced at least one major cardiovascular event (ie. heart attack, stroke, heart failure, or death from cardiovascular disease).

With every 5mmHg reduction in systolic blood pressure, the risk of developing major cardiovascular disease decreased by approximately 10% (18 287 vs 24 037 major cardiovascular disease in the intervention and comparator groups, respectively), stroke by 13% (6005 vs 7767), heart failure by 13% (3249 vs 4584), ischaemic heart disease by 8% (8307 vs 11 145), and  cardiovascular disease mortality by 5% (4 825 vs 6 110).

The beneficial effects of the treatment did not differ based on a history of having had cardiovascular disease or the level of blood pressure at study entry.

“It is important that people are considered for blood pressure-lowering treatment based on their cardiovascular risk, rather than focusing on blood pressure itself as a qualifying factor for or target of treatment,” said co-author Zeinab Bidel from the University of Oxford. “We must provide well-rounded guidelines to lower risks for cardiovascular disease that include exercise, nutrition, smoking cessation, and – where appropriate – medication.”

The study has some limitations, such as only investigating the impact of baseline blood pressure and prior cardiovascular disease on treatment effects, so the findings cannot be generalised to other patient characteristics that have not been included in the analysis.

Additionally, effects on diseases other than major cardiovascular disease, including potential treatment side effects, were not specifically examined.

Source: News-Medical.Net

Journal information: The Blood Pressure Lowering Treatment Trialists’ Collaboration., (2021) Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis. The Lancet. doi.org/10.1016/S0140-6736(21)00590-0.

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Cannabis Use Screening in Older People Urged

On By ModernMedia
Cannabis plants. Photo by Harrison Haines from Pexels

Older people who use cannabis to relieve or treat health conditions generally don’t discuss their substance use with doctors, according to a new study. 

In this study of over 17 000 people aged 50 and over in the US, some use cannabis daily and others have mental health problems. The findings were published in peer-reviewed The American Journal of Drug and Alcohol Abuse.

The research is the first to identify where older users obtain cannabis, with the majority saying obtaining it was easy. Those who use cannabis for health reasons are more likely than non-medical (recreational) users to buy it at a medical dispensary (20% vs 5%) and less likely to get it for free (25% vs 46%) or from other sources such as parties (49% vs 56%).

According to the authors, the findings have significant clinical and policy implications especially as more US states are legalising cannabis, which is leading to a rapid rise in uptake among older people. This has implications for other countries such as South Africa, which has recently decriminalised it for personal use.

They urge that doctors should be routinely screening older people for cannabis and other substance use, as well as checking cannabis users for mental health problems, and recommending treatment when necessary. They add that education on the risks of obtaining cannabis and cannabis products from unregulated sources is also vital for this group.

“Cannabis is readily available and accessible to older cannabis users for medical or non-medical purposes,” said Namkee G Choi from University of Texas.

“The findings suggest that some medical users may be self-treating without healthcare professional consultation.

“All older people who take cannabis should consult healthcare professionals about their use. As part of routine care, healthcare professionals should screen for cannabis and other substance use, and for mental health problems.

“They should also recommend services or treatment when indicated. Given the increase in THC (tetrahydrocannabinol) potency, healthcare professionals should educate older cannabis users, especially high-frequency users, on potential safety issues and adverse effects.”

THC content has increased significantly over the past decades. Since 1995, the potency of illicit cannabis plant material seized in the US has consistently increased over time, from approximately 4% in 1995 to approximately 12% in 2014. Among older US adults, cannabis has more than doubled between 2008 and 2019. Reasons include pain relief and treating health issues. However, not much is known about where they obtain cannabis and how much they discuss their use with doctors.

Data for the research was drawn responses from the 2018 and 2019 National Survey on Drug Use and Health (NSDUH), with 17 685 men and women aged 50 and older. This annual national survey measures substance use and misuse and mental illness across the US.

The researchers analysed responses including those on frequency of cannabis use, reasons for taking it, where it was obtained, and how much they utilised healthcare services.

The study found that, overall, 9% used cannabis over the past year and of these, 19% used cannabis for a medical purpose to some extent, eg, to treat chronic pain, depression or diseases like arthritis, while the rest (81%) were recreational (non-medical) users.

The authors also found that people who reported cannabis use as being for medical reasons were over four times as likely than non-medical users to discuss their use with a healthcare professional. Nevertheless, only a minority of medical users did so, which implies that some are self-treating without consulting a doctor.

Medical users were also more likely than non-medical users to more frequently take cannabis, with 40% using it between 200 and 365 days a year.

A higher proportion of older cannabis users had mental illness, alcohol use disorder, and nicotine dependence compared with non-users of the same age, although medical users were less likely to have alcohol problems compared to recreational users.

As well as calling on doctors to do more, the study authors say the NSDUH needs updating to “reflect changing cannabis product commercialization”, such as including products available to older people like cannabidiols, topical solutions and edibles.

Limitations of the study included the relatively small number of medical users and the fact some respondents may have under-reported their cannabis and other substance use.

Source: Medical Xpress

Journal information: The American Journal of Drug and Alcohol Abuse, www.tandfonline.com/doi/full/1 … 0952990.2021.1908318

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Study Explores the Circadian Rhythm Control Centre

On By ModernMedia
Woman sleeping with an alarm clock on bedside. Photo by cottonbro from Pexels

Researchers in Japan have offered new insights into how the brain’s circadian rhythm control centre regulates behaviour.

Circadian rhythms are a force in the background that shapes many human behaviours such feeling tired and falling asleep, as well as influencing our health. Michihiro Mieda and his team at Kanazawa University in Japan are researching just how the brain’s circadian rhythm control centre regulates behaviour.

The control centre, known as the superchiasmatic nucleus, or SCN, contains many types of neurons that transmit signals using the molecule GABA, but little is known about how each type contributes to our bodily rhythms. In this most recent study, the researchers focused on GABA neurons that produce arginine vasopressin, a hormone that regulates kidney function and blood pressure in the body, and which the team recently showed is also involved in the regulation of the interval of rhythms produced by the SCN.

To examine the function of these neurons separate to all others, the researchers first deleted a gene in mice which was needed for GABA signaling between neurons, but only in vasopressin-producing SCN neurons. “We removed a gene that codes for a protein that allows GABA to be packaged before it is sent to other neurons,” explained Mieda. “Without packaging, none of the vasopressin neurons could send out any GABA signals.”

Thus, these neurons could not use GABA to communicate with the rest of the SCN anymore. The mice showed longer periods of activity, beginning activity earlier and ending activity later than control mice, a simple enough result. It might seem that losing the packaging gene in the neurons disrupted the molecular clock signal but the result was not so simple. Closer examination deepened the mystery as the molecular clock seemed to progress unhindered.
Using calcium imaging, the researchers examined the clock rhythms within the vasopressin neurons. They found that while the rhythm of activity matched the timing of behaviour in control mice, this relationship was disturbed in the mice with missing GABA transmission in the vasopressin neurons. The rhythm of SCN output, ie SCN neuronal electrical activity, in the modified mice had the same irregular rhythm as their behaviour.

“Our study shows that GABA signaling from vasopressin neurons in the suprachiasmatic nucleus help fix behavioral timing within the constraints of the molecular clock,” concluded Mieda.

Source: News-Medical.Net

Journal reference: Maejima, T., et al. (2021) GABA from vasopressin neurons regulates the time at which suprachiasmatic nucleus molecular clocks enable circadian behavior. PNAS. doi.org/10.1073/pnas.2010168118.

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Loneliness in Middle-aged Men Tied to Cancer Risk

On By ModernMedia
Older man sitting alone on beach. Photo by Engin Akyurt from Pexels

A recent study by the University of Eastern Finland shows that loneliness among middle-aged men is associated with an increased risk of cancer.

Cancer is the second leading cause of death around the world, and in high-income countries it has become the main cause. Recent scientific evidence demonstrates that stress plays a positive role in cancer initiation, progression and cancer metastasis, as well as a negative role for anti-tumor immune function and therapy response.

“It has been estimated, on the basis of studies carried out in recent years, that loneliness could be as significant a health risk as smoking or overweight. Our findings support the idea that attention should be paid to this issue,” said project researcher Siiri-Liisi Kraav from the University of Eastern Finland.

The study was launched in the 1980s with middle-aged men from eastern Finland participating. To avoid reverse causality, individuals who already had a cancer diagnosis or received a cancer diagnosis within two years after the baseline data collection were excluded from the analysis. The  2570 eligible participants had their health and mortality monitored on the basis of register data through to the present. Follow-up lasted an average of 20.44 years, and the average age of cancer diagnosis was 69.96 years.
Factors accounted for included age, socio-economic status, lifestyle, sleep quality, depression symptoms, body mass index, heart disease and other risk factors.

During the follow-up, 649 men (25% of participants) developed cancer, and 283 men (11%) died of cancer. Loneliness was associated with a roughlt 10% increased cancer risk. In addition, cancer mortality was higher in cancer patients who were unmarried, widowed or divorced at baseline.
Based on these results, the researchers recommended that consideration of loneliness and social relationships should be an important part of comprehensive health care and disease prevention. The findings were published in Psychiatry Research.

“Awareness of the health effects of loneliness is constantly increasing. Therefore, it is important to examine, in more detail, the mechanisms by which loneliness causes adverse health effects. This information would enable us to better alleviate loneliness and the harm caused by it, as well as to find optimal ways to target preventive measures,” concluded Kraav.

Source: University of Eastern Finland

Journal information: Kraav, S., Lehto, S.M., Kauhanen, J., Hantunen, S., Tolmunen, T., 2021. Loneliness and social isolation increase cancer incidence in a cohort of Finnish middle-aged men. A longitudinal study. Psychiatry Research: https://doi.org/10.1016/j.psychres.2021.113868

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What is India’s ‘Double Mutant’ COVID Variant?

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Artistic rendering of SARS-CoV-2 virus, which causes COVID. Photo by CDC from Pexels

While Indian hospitals buckle under COVID cases and even capacity for cremations runs out, a new ‘double mutant’ variant of the virus has emerged.

First announced just one month ago, scientists are already trying to determine if it is driving the surge in Indian cases — and the implications for the rest of the world.

“We need to keep a close eye on this variant,” Katelyn Jetelina, PhD, MPH, of the University of Texas Health Science Center at Houston, wrote in a recent email newsletter.

What ‘double mutant’ means

Officially named B.1.617, the ‘double mutant’ is a bit of a misnomer, because it actually carries 13 mutations, 7 of which are in the spike protein. The nickname comes from two notable mutations found in other variants that appeared together for the first time in this new strain: the L452R and the E484Q mutations.

The L452R mutation in the spike protein was first found in the COVID variant detected in California, which could be up to 20% more transmissible than wild-type strains.

The E484Q mutation seems very similar to the E484K mutations found in the B.1.351 (South African) and P.1 (Brazilian) variants. These are ‘escape mutations’ because it enables these SARS-CoV-2 variants to evade immune protection with monoclonal antibodies, potentially making vaccines less effective. Thus far, current vaccines appear to be holding up against these variants, according to Jetelina.

The exact significance of these mutations is still being worked out.

“Just because there are two worrisome mutations on one variant doesn’t necessarily mean this is [doubly] contagious or [doubly] deadly. The WHO [World Health Organization] has declared B.1.617 a ‘Variant of Interest’ instead of a ‘Variant of Concern,'” she wrote.

The WHO definition of ‘variant of interest’ is one that has been found to cause community transmission, has been found in numerous COVID cases or clusters, or has been found in multiple countries. A ‘variant of concern’ on the other hand is defined as one that has been associated with or has demonstrated increased transmissibility, increased virulence, a change in clinical disease, or decreased effectiveness in treating or controlling the illness.

What is the significance of this variant?

The B.1.617 variant has spread rapidly in India, becoming the dominant strain in the state of Maharashtra in southwestern India. Maharashtra is India’s second most populous state and also home to India’s financial centre in Mumbai.

In December 2020, 271 million people (about one-fifth of India’s population) were already infected with COVID, and modelling studies suggested that natural infection had already caused India to reach herd immunity. In light of this, India’s health minister announced that the country had successfully contained the spread of the virus.

Yet three months later, the biggest COVID surge yet is happening in India, with a new high of over 340 000 new infections reported daily. Furthermore, experts believe the actual number of infections and deaths may be under-estimated.

Is the new variant possibly to blame for the current surge? Or is it a combination of factors related to people letting their guard down, such as a lack of masking, large gatherings of people mixing and travelling together, and a belief that somehow India was already immune?

No-one has answers to this yet, but a similar situation has already occurred elsewhere in the world.

“We saw the same story in Brazil. The city of [Manaus] had over 70% of people ‘naturally’ infected. But, once P.1. hit, they had a major surge,” Jetelina wrote. “Populations that have high ‘natural’ immunity are getting re-infected. It doesn’t look like natural infection will protect us for long. Get your vaccine.”

The variant has been found in the US and 18 other countries and on all continents, except Africa. Preliminary evidence so far suggests that the Covaxin vaccine, an inactivated virus vaccine made in India, is still protective against the double mutant variant. The trial attracted controversy since it was approved in January without a final phase III clinical trial. Scientists in India have also reported that Covishield, which is a viral vector vaccine like AstraZeneca’s jab, has efficacy against the mutant.

Dr Jetelina nevertheless urged vigilance: “The more this virus jumps from person-to-person (regardless of where it’s at in the globe), the more chances it has to mutate,” she wrote. “The more it mutates, the more chances it has to outsmart our vaccines.”

Source: MedPage Today