Day: December 13, 2022

Artificial Sweetener Found to Cause Anxiety-like Behaviour in Mice

Photo by Amit Lahav on Unsplash

Florida State University College of Medicine researchers have linked aspartame, an artificial sweetener found in nearly 5000 diet foods and drinks, to anxiety-like behaviour in mice.

Along with producing anxiety in the mice who consumed aspartame, the effects extended up to two generations from the males exposed to the sweetener. The study is published in the Proceedings of the National Academy of Sciences.

“What this study is showing is we need to look back at the environmental factors, because what we see today is not only what’s happening today, but what happened two generations ago and maybe even longer,” said co-author Pradeep Bhide, the Jim and Betty Ann Rodgers Eminent Scholar Chair of Developmental Neuroscience in the Department of Biomedical Sciences.

The study came about, in part, because of previous research from the Bhide Lab on the transgenerational effects of nicotine on mice. The research showed temporary, or epigenetic, changes in mice sperm cells. Unlike genetic changes (mutations), epigenetic changes are reversible and don’t change the DNA sequence; however, they can change how the body reads a DNA sequence.

“We were working on the effects of nicotine on the same type of model,” Bhide said. “The father smokes. What happened to the children?”

Aspartame received FDA approval as a sweetener in 1981. Today, nearly 5000 tonnes are produced each year. When consumed, aspartame becomes aspartic acid, phenylalanine and methanol, all of which can have potent effects on the central nervous system.

Led by doctoral candidate Sara Jones, the study involved providing mice with drinking water containing aspartame at approximately 15% of the FDA-approved maximum daily human intake. The dosage, equivalent to six to eight cans of diet fizzy drink a day for humans, continued for 12 weeks in a study spanning four years.

Pronounced anxiety-like behaviour was observed in the mice through a variety of maze tests across multiple generations descending from the aspartame-exposed males.

“It was such a robust anxiety-like trait that I don’t think any of us were anticipating we would see,” Jones said. “It was completely unexpected. Usually you see subtle changes.”

When given diazepam, a drug used to treat anxiety disorder in humans, mice in all generations ceased to show anxiety-like behaviour.

Researchers are planning an additional publication from this study focused on how aspartame affected memory. Future research will identify the molecular mechanisms that influence the transmission of aspartame’s effect across generations.

Source: Florida State University

Cardiovascular Risk from Extreme Hot and Cold Days

Source: Pixabay CC0

Extremely hot and cold temperatures both increased the risk of death among people with cardiovascular diseases, such as ischaemic heart disease, stroke, heart failure and arrhythmia, according to new research published today in journal Circulation.

Among the cardiovascular diseases examined in this study, heart failure was linked to the highest excess deaths from extreme hot and cold temperatures.

“The decline in cardiovascular death rates since the 1960s is a huge public health success story as cardiologists identified and addressed individual risk factors such as tobacco, physical inactivity, Type 2 diabetes, high blood pressure and others. The current challenge now is the environment and what climate change might hold for us,” said Barrak Alahmad, MD, MPH, PhD, research fellow at Harvard University and Kuwait University.

Researchers analysed health data for more than 32 million cardiovascular deaths that occurred in 567 cities in 27 countries on 5 continents between 1979 and 2019.

Climate change is associated with substantial swings in extreme hot and cold temperatures, so the researchers examined both in the current study. For this analysis, researchers compared cardiovascular deaths on the hottest and the coldest 2.5% of days for each city with cardiovascular deaths on the days that had optimal temperature (the temperature associated with the least rates of deaths) in the same city.

For every 1000 cardiovascular deaths, the researchers found that:

  • Extreme hot days accounted for 2.2 additional deaths.
  • Extreme cold days accounted for 9.1 additional deaths.
  • Of the types of heart diseases, the greatest number of additional deaths was found for people with heart failure (2.6 additional deaths on extreme hot days and 12.8 on extreme cold days).

“One in every 100 cardiovascular deaths may be attributed to extreme temperature days, and temperature effects were more pronounced when looking at heart failure deaths,” said Haitham Khraishah, MD, co-author of the study. “While we do not know the reason, this may be explained by the progressive nature of heart failure as a disease, rendering patients susceptible to temperature effects. This is an important finding since one out of four people with heart failure are readmitted to the hospital within 30 days of discharge, and only 20% of patients with heart failure survive 10 years after diagnosis.”

Researchers suggest targeted warning systems and advice for vulnerable people may be needed to prevent cardiovascular deaths during temperature extremes.

“We need to be on top of emerging environmental exposures. I call upon the professional cardiology organisations to commission guidelines and scientific statements on the intersection of extreme temperatures and cardiovascular health. In such statements, we may provide more direction to health care professionals, as well as identify clinical data gaps and future priorities for research,” Alahmad said.

The underrepresentation of data from South Asia, the Middle East and Africa limits the ability to apply these findings to make global estimates about the impact of extreme temperatures on cardiovascular deaths.

Source: American Heart Association

Pop Culture Highlights How Exercise Can Improve Mental Health

The workplace should take note

Photo by Ketut Subiyanto on Pexels

A quarter of employees in South Africa have been diagnosed with depression, with the country’s economic contributors aged 25 to 44 being most affected and taking more than 18 days off work as a result, according to a recent study conducted by the South African Depression and Anxiety Group (SADAG). “While treatment or talking to someone is advised when dealing with mental health issues, the importance of exercise and healthy living is taking centre stage across pop culture channels,” says Sarah Rice, Chief People Officer at Skynamo.

This was illustrated in the recently released documentary produced by Jonah Hill on Netflix called ‘Stutz’. While highlighting the power of talk therapy, Hill’s therapist, Phil Stutz, outlines various tools that he has developed to help people manage depression, including his ‘life force’ model.

“This is a three levelled pyramid focussing on aspects that drive us forward,” shares Rice, who refers to the film where Stutz says that your life force is the only thing that’s capable of guiding you when you’re lost. “The bottom level of the pyramid is your relationship with your physical body, the second is your relationship with other people and the top level is your relationship with yourself.”

“While we are the only ones who are responsible for our relationship with ourselves, considering the fact that we spend a large amount of time in the office, companies should think about offering activities to improve employees’ wellbeing such as forming a running club or introducing yoga classes. These activities should be built into the company calendar so that it gives people permission to do them and not feel like they’re taking away from work time,” explains Rice.

Not only does this assist with the exercise aspect but also gives colleagues the opportunity to form a real connection and bond with each other, she says. “Additionally, it shows that the business is really keen on providing employees with a work-life balance – something which is trumping salary as a priority for most professionals.”

“This will improve the company’s wellbeing too as it will result in increased employee productivityreduced absenteeismhigher quality work, and even an R83.40 return for every R20 the business invests in the physical and mental health of employees, not to mention a 14% increase in profitability,” points out Rice.

She notes that, luckily, international companies like Google, Accenture, Microsoft and Nike are recognising that physical health is part of mental health. “A number of South African companies such as Absa, Discovery, Alexander Forbes, Unilever and South African Breweries are tapping into this as well.”

Victoria Henry, Head of Group Marketing at Alphawave, a specialised technology investment group with 16 companies in its portfolio, of which Skynamo is a part, echoes this by saying, “Mental health has definitely moved up the agenda in the workplace. It’s good to see more and more companies taking this seriously. Happy and healthy employees are better employees. Supporting employee mental health can increase engagement and performance, so it’s important that companies are investing in this.”

To encourage corporates – as well as individuals – to get active and connected to each other, Skynamo, in partnership with Alphawave, will be sponsoring the third annual Skynamo CROSS CHALLENGE – South Africa’s biggest off-road triathlon. A crucial component of the event is the Skynamo Corporate Challenge where teams will get to cycle, run and swim for the chance to win prizes, bragging rights and a trophy to showcase in the office – not to mention a team building experience full of exhilarating adventure and healthy competition.

Jacques de Villiers, co-founder of event organising company Scuttle adds that being outdoors and exercising greatly enhances mental health, especially since this reduces employee screen time. “Funnily enough, 70% of employees say that they would exercise more if they spent less time at their computers.”

The Skynamo CROSS CHALLENGE will be taking place on Saturday, 25 February 2023 in Grabouw with races for all ages and fitness levels. The full race comprises a 1000m swim, 22km mountain bike ride and 7,2km trail run, while the sprint race is approximately half the distance. There are also race options available for kids.

In the lead up to the Skynamo CROSS CHALLENGE, teams can test their fitness levels and group dynamics at the Lomond and Franschhoek Cross Triathlons taking place in December 2022 and January 2023 respectively.

Rice concludes by saying, “To help employees’ mental health in 2023, businesses should be raising awareness around and encouraging healthy living. Employers need to see employees as whole people, not just as ‘work people’, and must support them in living their best lives.”

To register, or for more information, go to www.scuttle.co.za/scuttle-events/crosschallenge. Online entries close on 20 February 2023 and no entries will be taken at the event.

How to Prevent Dangerous Weight Loss in COVID Patients

Photo by Stephen Andrews on Unsplash

COVID infection often causes adipose atrophy, weight loss and cachexia, which significantly contribute to poor quality of life and mortality. Now, researchers at Karolinska Institutet have discovered that SARS-CoV-2 infection fuels blood vessel formation in fat tissues, thus revving up the body’s thermogenic metabolism. Blocking this process with an existing drug curbed weight loss in mice and hamsters that were infected with the virus, according to the study published in the journal Nature Metabolism.

“Our study proposes a completely new concept for treating COVID associated weight loss by targeting the blood vessels in the fat tissues,” says corresponding author Yihai Cao, professor at Karolinska Institutet.

The researchers examined how different types of fat, including brown fat and visceral and subcutaneous white fat, reacted when exposed to SARS-CoV-2 and how it impacted weight in mice and hamsters. They found that the animals lost significant amounts of weight in four days and that this weight loss was preceded by the activation of brown fat and the browning of both types of white fat. These fat tissues also contained more microvessels and high levels of a signaling protein called vascular endothelial growth factor (VEGF), which promotes the growth of new blood vessels.

Similar mechanisms in humans

The researchers observed the same mechanisms in human tissue samples from four patients who died of COVID, suggesting the findings could be clinically relevant for humans.

When the animals were treated with an anti-VEGF drug, the animals recovered most of their lost weight and their fat tissues exhibited fewer microvessels.

“Antiangiogenic drugs are currently used in the clinic to treat various types of cancers,” Yihai Cao says. “It’s possible these drugs could also be helpful in treating COVID-related problems such as excessive weight loss and metabolic changes, thus improving the quality of life and survival for these patients. Of course, we will need more research to validate if our preclinical findings also hold up in human trials.”

Source: Karolinska Institutet

New Immunotherapy Sees 73% Success Rate in Multiple Myeloma Patients

Woman using lab equipment
Source: NCI on Unsplash

A new immunotherapy to kill bone marrow cancer cells was successful in as many as 73% of patients in two clinical trials, according to Mount Sinai researchers. The new bispecific antibody therapy binds to both T cells and multiple myeloma cells and directs the T cells to kill multiple myeloma cells. The researchers described this strategy as “bringing your army right to the enemy.”

The success of the off-the-shelf immunotherapy, called talquetamab, was even seen in patients whose cancer resisted previous therapies. It uses a different target than other approved therapies: a receptor expressed on the surface of cancer cells known as GPRC5D.

Talquetamab was tested in phase 1 and phase 2 trials. The phase 1 trial, reported in NEJM, established two recommended doses that were tested in the phase 2 trial. The results of the phase 2 trial were reported at the American Society of Hematology annual meeting. The study participants had all received at least three different therapies without achieving lasting remission, suggesting talquetamab could offer new hope for patients with hard-to-treat multiple myeloma.

“This means that almost three-quarters of these patients are looking at a new lease on life,” said lead author of the studies, Ajai Chari, MD, Director of Clinical Research in the Multiple Myeloma Program at The Tisch Cancer Institute. “Talquetamab induced a substantial response among patients with heavily pretreated, relapsed, or refractory multiple myeloma, the second-most-common blood cancer. It is the first bispecific agent targeting the protein GPRC5d in multiple myeloma patients.”

Nearly all patients with myeloma who receive standard therapies continually relapse. Patients who relapse or become resistant to all approved multiple myeloma therapies have a poor prognosis, so additional treatments are urgently needed. This study, while an early-phase trial designed to detect tolerability and find a safe dose, is an important step in meeting that need.

This international Phase 1 clinical trial enrolled 232 patients between January 2018 and November 2021. Patients received a variety of doses of the therapy either intravenously or subcutaneously; future studies will focus on doses only administered subcutaneously either weekly or every other week

The efficacy and safety findings in the phase 1 study were validated in the phase 2 trial presented at ASH. The phase 2 trial included 143 patients treated on a weekly dose and 145 patients treated at a higher biweekly dose.

The overall response rate in these two groups was about 73%, Dr Chari said. The response rate was maintained throughout various subgroups examined, with the exception of patients with a rare form of multiple myeloma that also extends to organs and soft tissues. More than 30% of patients in both groups had a complete response (no detection of myeloma-specific markers) or better, and nearly 60% had a “very good partial response” or better (indicating the cancer was substantially reduced but not necessarily down to zero).

The median time to a measurable response was approximately 1.2 months in both dosing groups and the median duration of response to date is 9.3 months with weekly dosing. Researchers are continuing to collect data on the duration of response in the group receiving 0.8 mg/kg every other week and for patients in both dosing groups who had a complete response or better.

Side effects were relatively frequent, but typically mild. About three-quarters of patients experienced a common side effect of immunotherapy – cytokine release syndrome, a constellation of symptoms including fever. About 60% experienced skin-related side effects such as rash, about half reported taste changes, and about half reported nail disorders. Only 5–6% of patients stopped treatment due to side effects.

The response rate observed in the study, which Dr Chari explained is higher than that for most currently accessible therapies, suggests talquetamab could offer a viable option for patients whose myeloma has stopped responding to most available therapies, offering a chance to extend life and benefit from other new and future therapies as they are developed.

Source: Mount Sinai Hospital