Day: March 28, 2024

Positive Associations between Premenstrual Disorders and Perinatal Depression

Researchers utilise data from Swedish nationwide registers of over 900 000 women

Photo by Sydney Sims on Unsplash

Women affected by premenstrual disorders have a higher risk of perinatal depression compared with those who do not, according to research published March 28th in the open access journal PLOS Medicine. The relationship works both ways: those with perinatal depression are also more likely to develop premenstrual disorders after pregnancy and childbirth. This study suggests that a common mechanism might contribute to the two conditions.

Menstruating women experience cyclical hormone fluctuations through puberty, menstrual cycle, pregnancy and menopause. Some women have difficult to manage symptoms of low mood and depression during these fluctuations. Between a fifth and a third of women are reportedly affected by premenstrual disorders and 11% of mothers suffer perinatal depression – depressive symptoms during pregnancy and up to 12 months after delivery.

Qian Yang and colleagues at the Karolinska Institutet, Sweden and University of Iceland used the Swedish nationwide registers from 2001 to 2018 and identified 84 949 women with perinatal depression and 849 482 unaffected women. The researchers matched the women on age and calendar year, and further controlled for demographic factors, smoking, BMI, parity and history of psychiatric disorders. Among women with perinatal depression, almost 3% had premenstrual disorders before pregnancy compared with 0.6% of matched unaffected women. Women with perinatal depression were also twice as likely to report premenstrual disorders when the menstruation resumed after childbirth, compared to those unaffected by perinatal depression.

The research sheds light on the association between the two conditions and supports a theory that they may share underlying biological mechanisms and/or risk factors. Understanding this association could help healthcare providers to better target support to women most likely to be affected.

The authors add, “This study reveals a strong bidirectional relationship between perinatal depression and premenstrual disorders, using data from over 900 000 pregnancies. The findings suggest that both disorders may exist on a continuum, and emphasise the importance of recognising these susceptibilities in clinical practice.”

Provided by PLOS

Getting too Little Sleep Linked to High Blood Pressure

Photo by Andrea Piacquadio

Sleeping fewer than seven hours is associated with a higher risk of developing hypertension over time, according to a study presented at the American College of Cardiology’s Annual Scientific Session.

While the association between sleep patterns and hypertension has been reported, evidence about the nature of this relationship has been inconsistent, according to researchers. The current analysis pools data from 16 studies conducted between January 2000 and May 2023, evaluating hypertension incidence in 1 044 035 people from six countries without a prior history of hypertension over a median follow-up of five years (follow-up ranged from 2.4 to 18 years). Short sleep duration was significantly associated with a higher risk of developing hypertension after adjusting for demographic and cardiovascular risk factors, including age, sex, education, BMI, blood pressure, smoking status etc. Furthermore, the association was found to be even stronger for those getting less than five hours of sleep.

“Based on the most updated data, the less you sleep – that is less than seven hours a day – the more likely you will develop high blood pressure in the future,” said Kaveh Hosseini, MD, assistant professor of cardiology at the Tehran Heart Center in Iran and principal investigator of the study. “We saw a trend between longer sleep durations and a greater occurrence of high blood pressure, but it was not statistically significant. Getting seven to eight hours of sleep, as is recommended by sleep experts, may be the best for your heart too.”

The study found that sleeping less than seven hours was associated with a 7% increased risk of developing hypertension, which spiked to 11% when reported sleep duration was less than five hours. By comparison, diabetes and smoking are known to heighten one’s risk of hypertension by at least 20%, Hosseini said.

While the study did not look at why this might be the case, Hosseini said that disrupted sleep could be to blame. For example, he said lifestyle habits or comorbid conditions such as overeating, alcohol use, nightshift work, certain medication use, anxiety, depression, sleep apnoea or other sleep disorders may be factors.

Researchers were surprised there were no age-based differences in the association between sleep duration and hypertension given that sleep patterns tend to shift with age. Participants ranged in age from 35.4 years to 60.9 years and 61% were female. When compared with men, females who reported less than seven hours of sleep had a 7% greater risk of developing hypertension.

“Getting too little sleep appears to be riskier in females,” Hosseini said. “The difference is statistically significant, though we are not sure it’s clinically significant and should be further studied. What we do see is that lack of good sleep patterns may increase the risk of high blood pressure, which we know can set the stage for heart disease and stroke.”

It’s important for people to talk with their health care team about their sleep patterns, especially if they have disrupted sleep that might be due to obstructive sleep apnoea. Sleep apnoea has been tied to higher rates of high blood pressure, stroke and coronary artery disease.

This study has several limitations, including that sleep duration was based on self-reported questionnaires, so changes in sleep duration over the follow-up period were not assessed. Moreover, there were variations in how short sleep duration was defined between the studies (fewer than five or six hours).

“Further research is required to evaluate the association between sleep duration and high blood pressure using more accurate methods like polysomnography, a method for evaluating sleep quality more precisely,” Hosseini said. “Moreover, the variations in reference sleep duration underline the need for standardised definition in sleep research to enhance the comparability and generalisability of findings across diverse studies.”

Source: American College of Cardiology

Inaoside A, a New Antioxidant Derived from Mushrooms

Photo by Marek Piwnicki

Natural products have unique chemical structures and biological activities and can play a pivotal role in advancing pharmaceutical science. In a pioneering study, researchers from Shinshu University discovered Inaoside A, an antioxidant derived from Laetiporus cremeiporus mushrooms. This breakthrough, published in the journal Heliyon, sheds light on the potential of mushrooms as a source of therapeutic bioactive compounds.

The search for novel bioactive compounds from natural sources has gained considerable momentum in recent years due to the need for new therapeutic agents to combat various health challenges. Among a diverse array of natural products, mushrooms have emerged as a rich reservoir of bioactive molecules with potential pharmaceutical and nutraceutical applications. The genus Laetiporus has attracted attention for its extracts exhibiting antimicrobial, antioxidant, and antithrombin bioactivities. The species Laetiporus cremeiporus, spread across East Asia, has also been reported to show antioxidant properties. However, the identification and characterisation of specific antioxidant compounds from this species have not been conducted.

In a groundbreaking study, researchers led by Assistant Professor Atsushi Kawamura from the Department of Biomolecular Innovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, along with Hidefumi Makabe from the Department of Agriculture, Graduate School of Science and Technology, Shinshu University, and Akiyoshi Yamada from the Department of Mountain Ecosystem, Institute for Mountain Science, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, recently discovered the antioxidant compound derived from L. cremeiporus.

The researchers collected fresh fruiting bodies of L. cremeiporus from the Ina campus of Shinshu University. The obtained extracts were concentrated and partitioned between water and ethyl acetate. After this, the extracts were subjected to advanced chromatographic techniques, which led to the successful isolation of Inaoside A, a new antioxidant phenolic compound, along with three other well-characterised bioactive compounds, i.e., 5′-S-methyl-5′-thioadenosine (MTA), nicotinamide, and adenosine.

“Our study marks the pioneering discovery of Inaoside A from an extract of the edible mushroom Laetiporus cremeiporus. To date, there has been only one prior report on the biological function of an extract of L. cremeiporus. We are the first to uncover the isolation of an antioxidant compound from L. cremeiporus,” states Professor Kawamura, highlighting the breakthrough research.

Next, the researchers wanted to determine the structure of the newly found antioxidant compound. For this, they utilised one and two- dimensional NMR and other spectroscopic analyses. The structure of Inaoside A revealed a planar configuration. With a molecular formula of C17H24O7, the compound was found to feature a distinctive ribose moiety, identified as α-ribofuranoside through stereochemical analysis. Subsequent investigation into the absolute stereochemistry confirmed the D-ribose configuration, thereby reinforcing the planar structure of this compound.

The mushroom extracts were then isolated into fractions to determine the antioxidant activities of the four isolated bioactive compounds. These fractions were then examined by DPPH radical scavenging and superoxide dismutase assays. The findings were noteworthy as the DPPH radical scavenging activity exhibited by Inaoside A was significant, showing 80% inhibition at 100μg/mL, indicative of its significant antioxidant properties. The IC50 value of Inaoside A was determined to be 79.9μM, further highlighting its efficacy as an antioxidant agent.

What are the objectives of the researchers following the discovery of Inaoside? Professor Kawamura reveals, “We are now focusing on investigating the chemical compositions and biological properties of natural compounds obtained from mushrooms. Our goal is to uncover the potential of edible mushrooms as functional foods through this discovery.”

The identification of Inaoside A as an antioxidant from Laetiporus cremeiporus marks a significant breakthrough in natural product research, highlighting the potential of mushrooms as a source of therapeutic bioactive compounds. These findings may lead to the development of novel antioxidant-based therapies for various health conditions. Further studies should focus on synthetic research and detailed investigations into the biological activity of Inaoside A, aiming to harness its potential as a pharmaceutical lead compound.

Source: Shinshu University

Just Ask: Many Patients in the ED are Open to Flu Vaccination

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Simply asking patients to get the flu vaccine, and combining it with helpful video and print messages, is enough to persuade many who visit emergency departments to roll up their sleeves, according to a new study published in NEJM Evidence.

Researchers led by UC San Francisco found a 32% vaccine uptake in patients who were asked if they’d be interested in getting the flu shot and told their health providers would be informed.

They saw a 41% uptake for those who were asked about receiving a flu shot and received a pamphlet, watched a three-minute video of a physician with a similar ethnic background discussing the vaccine and were told about the benefits of the vaccine.

The researchers say this type of systematic approach could lead to more underserved people receiving vaccines, especially those whose primary health care occurs in emergency departments.

Flu can be fatal

Annual mortality rates from flu are typically in the tens of thousands in the U.S., especially when combined with pneumonia – but vaccination is particularly low among underserved populations and those whose primary care occurs in emergency departments.

Such patients often face general vaccine hesitancy or a lack of opportunities for the flu shot.

“This research arose from our desire to address the health disparities that we see every day in our emergency department, especially among homeless persons, the uninsured and immigrant populations,” said first author, Robert M. Rodriguez, MD, a professor of Emergency Medicine with the UCSF School of Medicine.

The researchers designed the clinical trial to span a single flu season between October 2022 and February 2023.

Investigators in the study created flu vaccine messaging – including a brief video, flyer and a scripted health provider question, “Would you be willing to accept the influenza vaccine?” – and assessed their effectiveness among nearly 800 patients in five cities: San Francisco, Houston, Philadelphia, Seattle and Durham, North Carolina.

The median age was 46, and more than half the participants in the trial were Black or Latino, 16 % lacked health insurance, nearly a third had no primary care and 9% were homeless or living in severely inadequate housing. These demographic characteristics are similar to patient populations often served by urban emergency departments.

“Overall, our study adds to the growing body of knowledge showing that a number of important public health interventions can and should be delivered to underserved populations in emergency departments,” said Rodriguez, whose previous research has found the effectiveness of delivering similar COVID-19 vaccine messaging to emergency department patients.

Source: University of California – San Francisco

Making Long-term Memories Requires DNA Damage and Brain Inflammation

Source: CC0

Just as you can’t make an omelette without breaking eggs, scientists at Albert Einstein College of Medicine have found that you can’t make long-term memories without DNA damage and inflammation in the brain. Their surprising findings were published online today in the journal Nature.

“Inflammation of brain neurons is usually considered to be a bad thing, since it can lead to neurological problems such as Alzheimer’s and Parkinson’s disease,” said study leader Jelena Radulovic, MD, PhD, professor of psychiatry and behavioural sciences at Einstein. “But our findings suggest that inflammation in certain neurons in the brain’s hippocampal region is essential for making long-lasting memories.”

The hippocampus has long been known as the brain’s memory centre. Dr Radulovic and her colleagues found that a stimulus sets off a cycle of DNA damage and repair within certain hippocampal neurons that leads to stable memory assemblies, ie clusters of brain cells representing past experiences.

From shocks to stable memories

The researchers discovered this memory-forming mechanism by giving mice brief, mild shocks sufficient to form an episodic memory of the shock event. Then, they analysed neurons in the hippocampal region and found that genes participating in an important inflammatory signalling pathway had been activated.

“We observed strong activation of genes involved in the Toll-Like Receptor 9 (TLR9) pathway,” said Dr Radulovic, who is also director of the Psychiatry Research Institute at Montefiore Einstein (PRIME). “This inflammatory pathway is best known for triggering immune responses by detecting small fragments of pathogen DNA. So at first we assumed the TLR9 pathway was activated because the mice had an infection. But looking more closely, we found, to our surprise, that TLR9 was activated only in clusters of hippocampal cells that showed DNA damage.”

Brain activity routinely induces small breaks in DNA that are repaired within minutes. But in this population of hippocampal neurons, the DNA damage appeared to be more substantial and sustained.

Triggering inflammation to make memories

Further analysis showed that DNA fragments, along with other molecules resulting from the DNA damage, were released from the nucleus, after which the neurons’ TLR9 inflammatory pathway was activated; this pathway in turn stimulated DNA repair complexes to form at an unusual location: the centrosomes. These organelles are present in the cytoplasm of most animal cells and are essential for coordinating cell division. But in neurons – which don’t divide – the stimulated centrosomes participated in cycles of DNA repair that appeared to organise individual neurons into memory assemblies.

“Cell division and the immune response have been highly conserved in animal life over millions of years, enabling life to continue while providing protection from foreign pathogens,” Dr. Radulovic said. “It seems likely that over the course of evolution, hippocampal neurons have adopted this immune-based memory mechanism by combining the immune response’s DNA-sensing TLR9 pathway with a DNA repair centrosome function to form memories without progressing to cell division.”

Resisting inputs of extraneous information

During the week required to complete the inflammatory process, the mouse memory-encoding neurons were found to have changed in various ways, including becoming more resistant to new or similar environmental stimuli. “This is noteworthy,” said Dr Radulovic, “because we’re constantly flooded by information, and the neurons that encode memories need to preserve the information they’ve already acquired and not be ‘distracted’ by new inputs.”

“This is noteworthy,” said Dr Radulovic, “because we’re constantly flooded by information, and the neurons that encode memories need to preserve the information they’ve already acquired and not be ‘distracted’ by new inputs.”

Importantly, the researchers found that blocking the TLR9 inflammatory pathway in hippocampal neurons not only prevented mice from forming long-term memories but also caused profound genomic instability, ie, a high frequency of DNA damage in these neurons.

“Genomic instability is considered a hallmark of accelerated aging as well as cancer and psychiatric and neurodegenerative disorders such as Alzheimer’s,” Dr Radulovic said.

“Drugs that inhibit the TLR9 pathway have been proposed for relieving the symptoms of long COVID. But caution needs to be shown because fully inhibiting the TLR9 pathway may pose significant health risks.”

PhD Student Elizabeth Wood and Ana Cicvaric, a postdoc in the Radulovic lab, were the study’s first authors at Einstein.

Source: Albert Einstein College of Medicine

Low Resting Heart Rate in Women is Associated with Criminal Offending, Injuries

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In women, a low resting heart rate is associated with a slightly raised incidence of criminal offending as well as of unintentional injuries, in a large all-female study published March 27 in the open-access journal PLOS ONE by Sofi Oskarsson of School of Behavioural, Social and Legal Sciences, Örebro University, Sweden, and colleagues. This is the first time such an association has been shown in women, although it is well established in studies of men.

Intervention efforts for crime tend to focus on structural and social factors as well as personality traits and behaviors. Less is known about biological factors, although there is an established association between the autonomic nervous system – a network of nerves that regulates unconscious body processes like breathing and heartbeat – and criminal offending in men. Sofi Oskarsson and colleagues from Örebro University, Sweden, wanted to see if the same is observed in women.

Using population registers, the team identified 12 500 Swedish women who volunteered for military service at around 18 years old, where physical assessments recorded resting heart rate and blood pressure. They also tracked records for violent and nonviolent criminal offences and unintentional injuries for up to 40 years.

Female conscripts with the lowest resting heart rates (under 69bpm) had 35% higher risk for any criminal conviction compared to those with rates above 83bpm. However, no significant associations were found for violent crime. Lower resting heart rate was associated with an increased risk of unintentional injuries, which in past research has been interpreted as potentially reflecting fearlessness and stimulation seeking tendencies. The team found a significant association between blood pressure and violent crime, but no significant association was found for non-violent crime. 

The authors state that low autonomic nervous system arousal might drive stimulation-seeking tendencies, but that their findings should be interpreted with caution. They saw lower rates of criminal offending compared to women who had not done military service, and a higher rate of unintentional injuries, so further work is needed to establish whether the same is seen in wider cohorts. If replicated by further research, this finding could have the potential to serve as a predictor of criminal offending, in women as well as men.

The authors add: “Our research reveals a compelling link between lower resting heart rate and an elevated risk of criminality and unintentional injuries among female conscripts. This association, previously underscored primarily in men, paves way for innovative strategies predicting crime risk among women.”

Earlier Puberty Onset in Girls may Affect Adult Cardiometabolic Health

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Experiencing puberty earlier, compared to same-age peers, may be one of the mechanisms through which childhood risk factors influence adult cardiometabolic health issues, according to a study published March 27, 2024 in the open-access journal PLOS ONE by Maria Bleil from the University of Washington, USA and colleagues.

Adverse experiences in childhood are frequently linked to poor health in adulthood. Most of the conceptual models describing adversity-related changes that may be adaptive to stress in the short-term but are risky to long-term health don’t specifically include puberty, which links childhood and adulthood and is itself also sensitive to the child’s environment. Earlier onset of puberty is often linked to factors like race (with Black and Latina girls developing earlier than White girls), mother’s age at her first period, infant weight gain and childhood obesity, and adverse experiences like childhood socioeconomic disadvantage, stressful parent-child relationships, and other stressful life events.

Here, Bleil and colleagues modeled pubertal timing and health risks in a cohort of women who had participated in the 30-year NICHD Study of Early Child Care and Youth Development prospective study of children and their families. Participants were followed from birth to adolescence (1991–2009) to examine trajectories of child health and development, with an additional in-person study follow-up (2018–2022) among participants ages 26 to 31 to capture social, behavioural, and health status information in adulthood. The authors fit models to data from the full sample of 655 women.

The authors found that later pubertal onset (later breast development, pubic hair onset, and first period) predicted lower adulthood cardiometabolic risk. These puberty indicators were also found to mediate the effects of factors like mother’s age at her first period, race, BMI percentile, and childhood socioeconomic status on adult cardiometabolic risk. 

It’s important to note that this study maps predictive relationships between childhood risk factors, timing of puberty, and adulthood cardiometabolic risks, but cannot prove causation. That said, the pattern of results provides strong longitudinal evidence for the role of puberty onset as a pathway linking early life exposures and adulthood cardiometabolic health – and suggests targeting puberty onset may improve health more broadly in at-risk girls. The authors hope future studies will both replicate their findings and better characterise the nature of the links identified here.

The authors add: “This study suggests the timing of pubertal development in girls is an important pathway through which early life risk factors, such as prepubertal body mass index and socioeconomic position, influence cardiometabolic health in adulthood. The implications of this work are that pubertal development and its timing should be considered, and potentially targeted, in efforts to improve cardiometabolic health.”