Tag: 25/10/22

Diet and Exercise for Obese Mothers Lowers Cardiovascular Risk in Infants

Holding a baby's hand
Photo by William-Fortunato on Pexels

A new study, published in the International Journal of Obesity, found that 3-year-old children were more likely to exhibit risk factors for future heart disease if their mother was clinically obese during pregnancy. A behavioural lifestyle intervention reduced this risk.

There is increasing evidence to suggest that obesity in pregnancy is associated with cardiometabolic dysfunction in children, and that serious cardiovascular disease may begin in the womb.

The UPBEAT trial, conducted at Guy’s and St Thomas’ NHS Foundation Trust, randomised women with obesity (a BMI of over 30 kg/m2) in early pregnancy to a diet and exercise intervention or to standard pregnancy care. The intervention included one-to-one counselling, restricting dietary intake of saturated fat, eating foods with a low glycaemic index such as vegetables and legumes, moderate and monitored physical activity and tools to record exercise. The intervention arm saw improvements in weight gain in pregnancy, physical activity, a healthier diet, and a healthier metabolic profile across pregnancy.

Follow-up of the children at age three showed that children of women with clinical obesity had evidence of cardiac remodelling, a risk factor for future cardiovascular disease. Changes included increased heart muscle thickness, elevated resting heart rate, evidence of early impairment to the heart’s relaxation function and increased sympathetic nerve activity compared to women of normal weight. The children of women who were allocated to the intervention arm were protected from these early changes in heart structure and function.

Study lead Dr Paul Taylor, from King’s College London, said: “Maternal obesity appears to adversely impact the developing foetal nervous system and foetal heart development which is apparent up to 3 years-of-age. A complex lifestyle intervention in pregnancy was associated with protection against cardiac remodelling in infants. We can hypothesise that these changes to the heart and its function will get worse over time, putting the child at increased risk of cardiovascular disease in the future.”

The study suggests that maternal obesity may have a lasting impact on the child’s cardiovascular health. Promoting dietary changes and physical activity during pregnancy may reduce this risk.

Source: King’s College London

Earlier Mammograms for Family History of Breast Cancer may be Unnecessary

Woman receiving mammogram
Source: National Cancer Institute

A new study reported in the journal Cancer reconsiders guidelines for when to start screening with mammograms if a woman has a first degree relative who was diagnosed with breast cancer.

Women with a first-degree family relative diagnosed with breast cancer, who are otherwise at average risk, are often advised to get screened 10 years earlier than the relative’s diagnosis age. However, there is little evidence to support the long-standing recommendation.

UC Davis Comprehensive Cancer Center researcher Diana Miglioretti joined Danielle Durham, with the Department of Radiology at University of North Carolina at Chapel Hill, and five other researchers on the study. They analysed data from the Breast Cancer Surveillance Consortium on screening mammograms conducted from 1996–2016 to evaluate when screenings should begin for women with a family history of breast cancer.

More than 300 000 women were included in the national study. Researchers compared cumulative 5-year breast cancer incidence among women with and without a first-degree family history of breast cancer by relative’s age at diagnosis and screening age.

“The study concluded that a woman with a relative diagnosed at or before age 45 may wish to consider, in consultation with her doctor, initiating screening 5–8 years earlier than their relative’s diagnosis age, rather than a decade earlier. That puts them at a risk that is equal to that of an average-risk woman who is age 50, which is the most recommended age for starting mammograms,” said Durham.

BRCA gene mutation carriers may benefit from starting screenings earlier. Women ages 30–39 with more than one first-degree relative diagnosed with breast cancer may wish to consider genetic counselling.

Increasing the age for initiating screening could reduce the potential harms of starting breast cancer screenings too early. These include increased radiation exposure and false positive results that require women to return to the clinic for diagnostic imaging and possibly invasive procedures, but do not result in a breast cancer diagnosis. The earlier a woman starts receiving mammograms, the more screenings they will undergo over their lifetime – and that increases the chances of experiencing these harms.

“Mammography also may not perform as well in younger women because they are more likely to have dense breasts which increase the difficulty of finding cancer on the images and results in more false-positives,” Miglioretti said.

Source: University of California – Davis Health

Earlier HIV Diagnosis and Treatment Improves Outcomes

HIV themed candle
Image by Sergey Mikheev on Unsplash

Compared to delaying antiretroviral treatment (ART) early in the course of HIV infection, an earlier start to ART when the immune system is stronger results in better long-term health outcomes, according to findings presented at the IDWeek Conference.

The findings are based on an extended follow-up of participants in the National Institutes of Health-funded Strategic Timing of Antiretroviral Treatment (START) study. In 2015, START demonstrated a 57% reduced risk of AIDS and serious non-AIDS health outcomes among participants who began ART when their CD4+ T-cell counts were greater than 500 cells/mm³ compared with those who did not begin ART until either their CD4+ counts fell below 350 cells/mm³ or they developed AIDS. Following the 2015 report of these findings, the participants in the deferred treatment arm were advised to begin ART.

The international START study proved the benefit of early ART initiation, but longer-term follow-up of 4446 participants was undertaken to determine whether the health benefits of early ART compared with deferred ART increased, remained constant, or declined after the participants in the deferred arm were advised to begin ART. The primary study endpoints included the number of participants who developed AIDS; those who developed serious non-AIDS health conditions, such as major cardiovascular disease, kidney failure, liver disease and cancer; and those who died.

For participants who began ART before the end of 2015, the median CD4+ cell count at the time of ART initiation was 648 cells/mm³ for the immediate arm and 460 cells/mm³ for the deferred arm. The analysis presented today compared the primary study endpoints before the end of 2015, with those in the extended follow-up period, from 2016–2021. In the latter period, most deferred-arm participants were taking ART. During the second period, people initiating ART in the deferred group had rapid and sustained declines in HIV viral load (less than or equal to 200 copies/mL); however, CD4+ cell counts remained, on average, 155 cells lower compared with that of individuals in the immediate ART group.

While the risk of serious health outcomes was substantially diminished soon after ART was initiated in the deferred treatment group, some excess risk remained compared with the immediate treatment group. The deferred ART group continued to have a somewhat greater risk (21%) of serious health consequences or death in comparison to the immediate treatment group. Over the five-year follow-up, there were 27 cases of AIDS in the deferred group compared with 15 cases in the early group. Similarly, 88 cases of serious non-AIDS health issues occurred in the deferred treatment arm compared with 76 cases in the immediate treatment arm. Lastly, there were 57 deaths in the deferred treatment group compared to 47 in the immediate treatment arm.

These findings confirm that ART significantly improves the health of an individual with HIV and reduce the person’s risk of developing AIDS and serious health issues, and that early diagnosis and treatment are key to maximising these benefits and reducing risk, according to the presenters.

Source: NIH/National Institute of Allergy and Infectious Diseases

Signalling Control Explains Why Adult Hearts Cells Don’t Regenerate

Source: Pixabay CC0

New research published in Developmental Cell has uncovered a possible explanation for why explain why adult heart cells lack regeneration capacity. As heart cells mature in mice, the number of communication pathways called nuclear pores dramatically decreases. While this might protect the organ from damaging signals, it could also prevent adult heart cells from regenerating, the researchers found.

The study, from University of Pittsburgh and UPMC scientists, suggests that quieting communication between heart cells and their environment protects this organ from harmful signals related to stresses such as high blood pressure, but at the cost of preventing heart cells from receiving signals that promote regeneration.

“This paper provides an explanation for why adult hearts do not regenerate themselves, but newborn mice and human hearts do,” said senior author Bernhard Kühn, MD, professor of paediatrics. “These findings are an important advance in fundamental understanding of how the heart develops with age and how it has evolved to cope with stress.”

While skin and many other tissues of the human body retain the ability to repair themselves after injury, the same isn’t true of the heart. During human embryonic and foetal development, heart cells undergo cell division to form the heart muscle. But as heart cells mature in adulthood, they enter a terminal state in which they can no longer divide.

To understand more about how and why heart cells change with age, Prof Kühn teamed up with fellow Pitt researchers to look at nuclear pores. These perforations in the lipid membrane that surround a cell’s DNA regulate the passage of molecules to and from the nucleus.

“The nuclear envelope is an impermeable layer that protects the nucleus like asphalt on a highway,” said Prof Kühn. “Like manholes in this asphalt, nuclear pores are pathways that allow information to get through the barrier and into the nucleus.”

Using super-resolution microscopy, the researchers visualised and counted the number of nuclear pores in mouse heart cells, or cardiomyocytes. The number of pores decreased by 63% across development, from an average of 1,856 in foetal cells to 1040 in infant cells to just 678 in adult cells. These findings were validated with electron microscopy to show that nuclear pore density decreased across heart cell development.

In previous research, Prof Kühn and his team showed that a gene called Lamin b2, which is highly expressed in newborn mice but declines with age, is important for cardiomyocyte regeneration.

In the new study, they show that blocking expression of Lamin b2 in mice led to a decrease in nuclear pore numbers. Mice with fewer nuclear pores had diminished transport of signalling proteins to the nucleus and decreased gene expression, suggesting that reduced communication with age may drive a decrease in cardiomyocyte regenerative capacity.

“These findings demonstrate that the number of nuclear pores controls information flux into the nucleus,” explained Prof Kühn. “As heart cells mature and the nuclear pores decrease, less information is getting to the nucleus.”

In response to stress such as high blood pressure, a cardiomyocyte’s nucleus receives signals that modify gene pathways, leading to structural remodelling of the heart. This remodelling is a major cause of heart failure.

The researchers used a mouse model of high blood pressure to understand how nuclear pores contribute to this remodelling process. Mice that were engineered to express fewer nuclear pores showed less modulation of gene pathways involved in harmful cardiac remodelling. These mice also had better heart function and survival than their peers with more nuclear pores.

“We were surprised at the magnitude of the protective effect of having fewer nuclear pores in mice with high blood pressure,” said Prof Kühn. “However, having fewer communication pathways also limits beneficial signals such as those that promote regeneration.”

Source: University of Pittsburgh

Limpopo Measles Outbreak Continues amid Low Vaccination Rates

Photo by CDC on Unsplash

Since 11 October 2022, the National Institute for Communicable Diseases (NICD) seven measles cases have been detected in Greater Sekhukhune District in Limpopo province within 30 days, as of 21 October. 

Infected individuals ranged from 9 months to 24 years. One child was fully vaccinated for measles, with two measles doses given in 2019. One child was unvaccinated, and the other five measles cases had unknown vaccination history. One measles case was hospitalised while one other had a complication that led to pneumonia.

District and provincial health officials have started a public health response. This includes enhanced surveillance for measles, contact tracing, screening for suspected cases using a case definition followed by collection of blood and throat swabs for measles diagnostic testing, and reviewing medical records to pick up missed cases. Vaccinations are underway for those exposed to suspected or confirmed cases.

The measles immunisation coverage data for the Greater Sekhukhune district showed a decrease of 87% to 64% for measles dose 1 and 86% to 60% for measles dose 2 from 2017 to 2022. This is below the 95% coverage needed to achieve herd immunity. A survey is being done to validate the vaccination data provided to the province and investigate factors that might be contributing to the measles outbreak.  Community awareness and health promotion by healthcare workers is continuing in the district to inform the public about the spread of measles and interventions to prevent disease. Measles vaccination has been initiated for children under 15 years to increase the measles immunity in the community and to prevent further spread of measles.

Clinicians should continue to be on the alert for measles cases, especially in Limpopo Province, as large measles outbreaks are occurring in sub-Saharan Africa, including in neighbouring countries.

Signs and Symptoms

Measles is a highly contagious disease caused by a virus of the paromyxovirus family. Patients with measles present with fever and a rash. The rash looks like small, red, flat spots over the body. The rash does not form blisters, nor is it itchy or painful. Other signs include cough, conjunctivitis and coryza. Complications of measles can include diarrhoea, dehydration, encephalitis, blindness and death. Other measles complications are pneumonia, scarring of the cornea (kerato-conjunctivitis), and rarely encephalitis. Complications are more serious in very young children (under 2 years) or who are malnourished.

Clinicians and caregivers should check children’s road-to-health booklets to ensure measles vaccinations are up to date. Suspected measles cases should be notified on the NMC system. Click here to access the Case Notification form 

Source: NICD