Tag: 20/2/23

AI Finds Face Shape Changes in Children with in Utero Alcohol Exposure

Photo by Helena Lopes on Pexels

Using artificial intelligence, researchers have found a link between alterations in the shape of young children’s faces and the amount of alcohol their mothers drank, before and during pregnancy. Even alcohol in small amounts – 12g a week, or less than one glass of wine – made a difference.

The study, published in Human Reproductionis the first to detect this association in the children of mothers who drank alcohol up to three months before becoming pregnant but stopped during pregnancy.

The finding is important because the shape of children’s faces can be an indication of health and developmental problems.

Study leader Gennady Roshchupkin, assistant professor at Erasmus Medical Centre, Rotterdam, said: “I would call the face a ‘health mirror’ as it reflects the overall health of a child. A child’s exposure to alcohol before birth can have significant adverse effects on its health development and, if a mother regularly drinks a large amount, this can result in foetal alcohol spectrum disorder, FASD, which is reflected in children’s faces.”

FASD is defined as a combination of growth retardation, neurological impairment and recognisably abnormal facial development. Symptoms include cognitive impairment, attention deficit hyperactivity disorder (ADHD), learning difficulties, memory problems, behavioural problems, and speech and language delays. FASD is already known to be caused by a mother’s drinking during pregnancy, particularly heavy drinking. However, until now, little was known about the effect of low alcohol consumption on children’s facial development and, therefore, their health. This is also the first study to examine the question in children from multiple ethnic backgrounds.

The researchers used AI and deep learning to analyse three-dimensional images of children taken at the ages of nine (3149 children) and 13 (2477 children). The children were part of an ongoing population-based study of pregnant women and their children from foetal life onwards. The children in this analysis were born between April 2009 and January 2006.

“The face is a complex shape and analysing it is a challenging task. 3D imaging helps a lot, but requires more advanced algorithms to do this,” said Prof Roshchupkin. “For this task, we developed an AI-based algorithm, which takes high-resolution 3D images of the face and produce 200 unique measurements or ‘traits’. We analysed these to search for associations with prenatal alcohol exposure and we developed heat maps to display the particular facial features associated with the mothers’ alcohol consumption.”

Information on the mothers’ alcohol consumption was gained from questionnaires completed by the women in early, mid-, and late pregnancy. The researchers divided them into three groups: mothers who did not drink before or during pregnancy, mothers who drank during the three months before becoming pregnant but stopped when they became pregnant, and mothers who drank during pregnancy, including those who only drank during the first trimester of pregnancy, and those who continued to drink throughout pregnancy.

“We found a statistically significant association between prenatal alcohol exposure and face shape in the nine-year-old children. The more alcohol the mothers drank, the more statistically significant changes there were. The most common traits were turned-up nose tip, shortened nose, turned-out chin and turned-in lower eyelid,” said Mr Xianjing Liu, first author of the study and a PhD student in Prof Roshchupkin’s group, who developed the AI algorithm.

“Among the group of mothers who drank throughout pregnancy, we found that even if mothers drank very little during pregnancy, less than 12g a week, the association between alcohol exposure and children’s facial shape could be observed. This is the first time an association has been shown at such low levels of alcohol consumption.”

At older ages, the alcohol consumption and face shape association weakened. No significant association was found when the researchers looked at data for the children at the age of 13 years.

“It is possible that as a child ages and experiences other environmental factors, these changes may diminish or be obscured by normal growth patterns. But that does not mean that alcohol’s effect on the health will also disappear. Therefore, it is crucial to emphasise that there is no established safe level of alcohol consumption during pregnancy and that it is advisable to cease drinking alcohol even before conception to ensure optimal health outcomes for both the mother and the developing foetus,” said Prof. Roshchupkin. “Further investigations on the mechanism of association are needed to fully understand how the association develops and then weakens with age.”

In the nine-year-olds, researchers found statistically significant facial traits were associated with mothers’ alcohol consumption when they compared those who drank before pregnancy but stopped on becoming pregnant with mothers who continued drinking throughout pregnancy.

They also looked at data for women who drank during the first trimester but then stopped, and those who continued to drink. The results were similar, which suggests that the associations were explained mainly by the foetus’s exposure to alcohol in the first three months of pregnancy.

According to the researchers, previous studies of childhood development after prenatal exposure to alcohol have suggested that possible mechanisms of action may be metabolic disorders in the mothers, such as problems with blood sugar levels and fatty liver disease, and that this could also explain the link with face shape. However, further investigations are needed.

The large number of children from multiple ethnic backgrounds is a strength of the study. Limitations include that there were no data on alcohol consumption more than three months before pregnancy, and that mothers may not have completed the questionnaire about their drinking habits correctly, possibly underestimating their consumption. Causation also cannot be established in this observational study.

Our Hospital can’t Cope, Say Atlantis Residents

By Peter Luhanga for GroundUp

People living in Atlantis, Cape Town, say they are struggling to access healthcare. There are two clinics run by the City – Saxon Sea and Protea Park – offering limited care, concentrating on family planning, child health, basic antenatal care, and HIV care. For any other health issues, residents have to go to Wesfleur Hospital. People queue for treatment as early as 5am.

In 2017, we wrote about the long queues and other problems at Wesfleur Hospital.

Community activists have set up the Atlantis Community Health Organisation (ACHO), which submitted a memorandum of grievances in August last year to Western Cape MEC for Health Nomafrench Mbombo, and resident Allison Adams, (not part of the ACHO) set up an online petition that has garnered over 1,275 signatures.

Adams and ACHO want the two City clinics taken over by the province so that they can be upgraded to offer primary and not just general healthcare. This would take pressure off Wesfleur.

“Clinics would serve as a conduit to relieve the hospital from everyday attendance. The hospital can’t cope. We have limited number of doctors available every day,” says Ashley Poole of ACHO.

Adams says the doctors can’t cope with treating patients, doing ward rounds and conducting medical assessments for residents seeking disability grants. It takes days for people to get help at the hospital, she says, and everyone with even a minor illness has to go to the hospital.

“We have people traveling to Dunoon Community Health Center to seek medical attention,” she says.

ACHO wants a new hospital built in Atlantis, which in the 2011 Census already had nearly 70,000 people.

Mayoral committee member for health Patricia van der Ross said the City is open to transferring the clinics, but “the Western Cape health department must have the requisite budget available to continue running the clinics”. Then a handover agreement can be concluded.

She said a task team was established and “numerous meetings” were held explaining to the community the challenges involved in doing such a transfer.

One interim measure is that stable, chronic patients are seen at Protea Park three days a week on Mondays, Thursdays and Fridays between 8am and 4pm, and at Saxonsea clinic on Mondays between 8am and 1pm.

Provincial health department spokesperson Natalie Watlington said since receiving the memorandum in August 2022, the department’s district team has implemented short and medium-term interventions to improve matters at Wesfleur Hospital.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp

Receptor Location is Key when Rebuilding Neural Connections with Psychedelic Drugs

Source: Pixabay CC0

When using psychedelic drugs to treat mental illness, it’s all down to location when rapidly rebuilding connections between nerve cells. In their paper published in Science, scientists show that engaging serotonin 2A receptors inside neurons promotes growth of new connections – but engaging the same receptor on the surface of nerve cells does not.

The findings will help guide efforts to discover new drugs for depression, PTSD and other disorders, according to senior author David E. Olson, associate professor at the University of California, Davis.

Drugs such as LSD, MDMA and psilocybin show great promise for treating a wide range of mental disorders that are characterised by a loss of neural connections. In laboratory studies, a single dose of these drugs can cause rapid growth of new dendrites from nerve cells, and formation of new spines on those dendrites.

Olson calls this group of drugs “psychoplastogens” because of their ability to regrow and remodel connections in the brain.

Earlier work from Olson’s and other labs showed that psychedelic drugs work by engaging the serotonin 2A receptor (5-HT2AR). But other drugs that engage the same receptor, including serotonin, do not have the same growth effects.

Maxemiliano Vargas, a graduate student in Olson’s lab, Olson and colleagues experimented with chemically tweaking drugs and using transporters to make it easier or harder for compounds to slip across cell membranes. Serotonin itself is polar, meaning it dissolves well in water but does not easily cross the lipid membranes that surround cells. The psychedelics, on the other hand, are much less polar and can easily enter the interior of a cell.

They found that the growth-promoting ability of compounds was correlated with the ability to cross cell membranes.

Drug receptors are usually thought of as being located on the cell membrane, facing out. But the researchers found that in nerve cells, serotonin 2A receptors were concentrated inside cells, mostly around a structure called the Golgi body, with some receptors on the cell surface. Other types of signalling receptors in the same class were on the surface.

The results show that there is a location bias in how these drugs work, Olson said. Engaging the serotonin 2A receptor when it is inside a cell produces a different effect from triggering it when it is on the outside.

“It gives us deeper mechanistic insight into how the receptor promotes plasticity, and allows us to design better drugs,” Olson said.

Source: University of California – Davis

Promising Results for Immunotherapy Drug Nivolumab in Advanced Skin Cancer

Female scientist in laboratory
Photo by Gustavo Fring on Pexels

A phase II clinical trial has demonstrated that patients with advanced cutaneous squamous cell carcinoma can benefit from the immune checkpoint inhibitor nivolumab. The findings were published in the journal CANCER

Two other immune checkpoint inhibitors, cemiplimab and pembrolizumab, have been approved by the US Food and Drug Administration for the treatment of advanced cutaneous squamous cell carcinoma in recent years. This new study is the first to report clinical trial results for nivolumab. 

The single-arm trial included 24 patients who received nivolumab at 3mg/kg every two weeks until they experienced cancer progression, developed unacceptable toxicity, or had received 12 months of treatment.  

During the trial, 14 patients (58.3%) benefited from the treatment, with their cancers demonstrating a response. Treatment-related adverse events of any grade occurred in 21 patients (87.5%) and, for and grade ≥ 3, in six patients (25%). One patient discontinued nivolumab due to toxicities. Prior radiotherapy exposure was associated with a worse response. 

“This is the first study to investigate nivolumab in this patient population, and it provides further evidence supporting the use of immune checkpoint blockers as standard therapies in cutaneous squamous cell carcinoma,” said lead author Rodrigo R. Munhoz, MD, of the Hospital Sírio-Libanês, in Brazil. 

An accompanying editorial notes that although the trial was small, its results were similar to those reported with pembrolizumab and cemiplimab. “In addition to providing more assurance to the clinical activity of different [immune checkpoint] inhibitors in this disease, this replicated data may permit a more widespread utilisation of these agents in managing a common disease with global implications,” the authors wrote. 

Source: Wiley

Self-stigma Linked to Worse Blood Glucose Control in Type 1 Diabetes

Diabetes - person measures blood glucose
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Because of their illness, patients with chronic medical conditions may experience self-stigma, or negative beliefs, emotional reactions, and behaviours towards themselves. New research published in the Journal of Diabetes Investigation found a link between self-stigma and glycated haemoglobin (HbA1c) in adults with type 1 diabetes.

The study included 109 adults in Japan with type 1 diabetes who completed questionnaires that generated scores based on a self-stigma scale. Although the findings support a link between self-stigma and sub-optimal HbA1c, additional studies are needed to show whether this is a causal relationship.

“We focused on this issue through clinical experiences with people with type 1 diabetes, whose glycaemic management improved markedly by social supports of eliminating diabetes-related stigma. Although the finding of an association between self-stigma and HbA1c is significant, further longitudinal research is required to determine whether self-stigma leads to sub-optimal HbA1c,” said corresponding author Yukiko Onishi MD, PhD, of the Institute of Medical Science, Asahi Life Foundation, in Tokyo. “This research does support and highlight the importance of eliminating self-stigma when treating people with type 1 diabetes.”

Source: Wiley

Some Dipeptides Found in Meat are Potent Antioxidants

Photo by Jose Ignacio Pompe on Unsplash

Imidazole dipeptides (IDPs), which are abundant in meat and fish, have been reported to be effective in relieving fatigue and preventing dementia. Researchers have discovered that most of these IDPs identified in beef, chicken and pork also have remarkably high antioxidant activity. They detailed their findings in the journal Antioxidants.

Professor Hideshi Ihara from the Osaka Metropolitan University Graduate School of Science led a research team that was the first to discover 2-oxo-imidazole-containing dipeptides (2-oxo-IDPs), which have one more oxygen atom than normal IDPs. Found at concentrations of  0.015–0.11% that of normal IDPs, these were also shown to be potent antioxidants.

In their study, the researchers came up with a method for selective and highly sensitive detection of five types of 2-oxo-IDPs using mass spectrometry, which enables quantitative detection of trace 2-oxo-IDPs in living organisms. Using this method, they revealed for the first time that beef, pork, chicken, and other meats contain antioxidants, not only IDPs but a variety of different 2-oxo-IDPs.

“We hope that this research method, which enables advanced analysis of 2-oxo-IDPs, will be applied not only to basic biology but also to medicine, agriculture, and pharmacy, where it will help improve peoples’ health and prevent diseases,” concluded Professor Ihara.

Source: Osaka Metropolitan University

A Regimen of Boiled Peanuts Desensitises Allergy Sufferers

Researchers took advantage of the fact that heat can affect the structure and immunoreactivity of peanuts, and tested out a peanut allergy therapy for children using sequential doses of boiled peanuts followed by roasted peanuts. Their trial, which is published in Clinical & Experimental Allergy, generated promising results, with 80% of participants experiencing desensitisation.

For this open-label, phase 2, single-arm clinical trial, 70 children aged 6–18 years old with peanut allergies received 12-hour boiled peanuts for 12 weeks, 2-hour boiled peanuts for 20 weeks, and roasted peanuts for 20 weeks, to a target maintenance dose of 12 roasted peanuts daily.

Fifty-six of the 70 (80%) participants became desensitised to peanuts. Treatment-related adverse events were reported in 43 (61%) participants, of whom three withdrew from the trial.

“Oral immunotherapy using boiled followed by roasted peanuts represents a pragmatic approach that appears effective in inducing desensitisation and is associated with a favourable safety profile,” the authors wrote.

Source: Wiley