Day: September 21, 2022

Categories : COVID Obstetrics & GynaecologyTags : Leave a comment

COVID Damages Placenta’s Immune Response

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In a study published in the American Journal of Obstetrics & Gynecology, researchers found that, if a woman is infected by SARS-CoV-2 during her pregnancy, the infection damages the placenta’s immune response to further infections – even if the infection was mild.

“This is the largest study to date of placentas from women who had COVID during their pregnancies,” said Professor Kristina Adams Waldorf, at the University of Washington School of Medicine and senior author of the study. “We were surprised to find that women who had COVID during their pregnancies had placentas with an impaired immune response to new infection.”

This finding, Prof Adams Waldorf added, “was the tip of the iceberg” in how COVID might affect foetal or placental development.

During the early stages of the pandemic, many thought that COVID did not appear to harm the developing foetus because there were so few babies born with COVID infection, she noted.

“But what we’re seeing now is that the placenta is vulnerable to COVID-19, and the infection changes the way the placenta works, and that in turn is likely to impact the development of the foetus,” Prof Adams Waldorf said.

“To date, the studies about how COVID might affect foetal or child development are very limited as the children are still very young,” noted co-author Dr Helen Feltovich, professor at Intermountain Healthcare.

“Our study suggests that babies born to mothers infected with COVID at any point during their pregnancy will need to be monitored as they grow up,” she said.

Studies led by Adams Waldorf have shown that pregnant women who contract COVID have a significantly higher mortality rate than those who do not contract COVID. Other studies have found that pregnant women are more likely to risk hospitalisations or preterm birth, according to the Center for Disease Control and Prevention.

It’s unknown how different COVID variants may affect the mother or foetus, Profs Adams Waldorf and Feltovich agree.

“Studying each of the variants in real time is really challenging because they just keep coming so fast, we can’t keep up,” Prof Adams Waldorf said. “We do know that the COVID Delta variant was worse for pregnant individuals, because there was a spike in stillbirths, maternal deaths and hospitalisations at that time.”

Regardless of the variant, Prof Adams Waldorf stressed taking precautions, such as vaccination and booster shots, limiting social contact a bubble of vaccinated individuals even if it means isolating for the duration of the pregnancy.

“The disease may be mild, or it may be severe, but we’re still seeing these abnormal effects on the placenta,” she said. “It seems that after contracting COVID in pregnancy, the placenta is exhausted by the infection, and can’t recover its immune function.”

In this study, a total of 164 pregnant individuals were studied, consisting of 24 uninfected healthy patients as a control group and 140 individuals who contracted COVID. Both groups delivered at about the same time, 37 to 38 weeks. Preterm birth occurred at nearly three times the rate with the patients with COVID when compared with those without. About 75% of the COVID patients had either asymptomatic COVID or mild symptoms.

Source: University of Washington School of Medicine/UW Medicine

Categories : Diseases, Syndromes and Conditions Metabolic DisordersTags : Leave a comment

New Study Explains Diabetes and UTI Link

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Huge clumps of E. coli (red) infecting diabetic mouse bladder. Photo: Soumitra Mohanty

Lower immunity and recurring infections are common in type 1 and type 2 diabetes. Research has shown that the immune system of people with diabetes has lower levels of the antimicrobial peptide psoriasin, which compromises the urinary bladder’s cell barrier, increasing the risk of urinary tract infection. The study is published in Nature Communications.

One effect of diabetes is that it compromises the innate immune system, leaving many people with increased susceptibility to regular infections, such as urinary tract infections (UTI)s caused by E. coli bacteria. In people with diabetes, these are more likely to lead to general blood poisoning, sepsis, originating in the urinary tract.

An endogenous antibiotic

Karolinska Institutet researchers investigated whether glucose levels in people with diabetes (type 1, type 2, or prediabetes) are linked with psoriasin, an endogenous antibiotic which is a part of the innate immune system.

Using samples of urine, bladder cells and blood serum from patients, the researchers analysed levels of psoriasin and other peptides necessary for ensuring that the bladder mucosa remains intact and protects against infection. The findings were then verified in mice and urinary bladder cells with and without infection.

“We found that high glucose concentrations reduce the levels of the antimicrobial peptide psoriasin, while insulin has no effect,” said Professor Annelie Brauner, who led the study. “People with diabetes have lower levels of psoriasin, which weakens the cells’ protective barrier function and increases the risk of bladder infection.”

Oestrogen therapy reduced bacterial population

Professor Brauner’s research group has previously shown that oestrogen restores the protective function of bladder cells in humans and mice and thereby help to regulate the immune response to a UTI. The researchers therefore tested how oestrogen treatment affects infected cells exposed to high glucose concentrations. They found that the treatment boosted levels of psoriasin and reduced bacterial populations, indicating that the treatment may have an effect also among patients with diabetes.

“We now plan to probe deeper into the underlying mechanisms of infections in individuals with diabetes,” said lead author Soumitra Mohanty. “The ultimate goal is to reduce the risk of infection in this growing patient group.”

Source: Karolinska Institutet

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International Gaucher Day on 1 October Highlights Need For Greater Attention on Rare Diseases

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Currently, there are an estimated 6000–8000 rare diseases, which affect 350 million people worldwide.1 One such rare condition is Gaucher Disease (GD) – a lysosomal storage disorder (LSD).  GD is a rare genetic disorder, passed down from parents to children (inherited) in an autosomal recessive manner. 

GD is one of the most common LSDs with a prevalence in the general population of ~1 per 100 000 and ~1/855 in the Ashkenazi Jewish population.2 As with many rare conditions, diagnosis of GD may present a significant challenge to non-GD specialities, owing to the wide variability in age, severity, type of clinical manifestation and lack of awareness of the early signs and symptoms of GD among non-specialist physicians.3 One in 6 patients with GD reported a diagnosis delay of 7 years or more after first consulting a doctor.3

International Gaucher Day on 1 October, therefore, aims to improve patients’ quality of life through greater awareness and earlier diagnosis of GD amongst healthcare professionals.

GD arises from an inherited deficiency of an enzyme called glucocerebrosidase, normally found within the lysosomes of cells, due to mutations in the GBA gene.4 This enzyme is responsible for breaking down a fatty substrate, glucocerebroside, into glucose and a simpler fat molecule (ceramide).4 Patients with GD have a progressive build-up of glucocerebroside within the lysosomes, particularly of macrophages, resulting in enlarged cells known as ‘Gaucher’ cells.4

These ‘Gaucher’ cells accumulate in organs throughout the body, predominately affecting the bone marrow, liver, and spleen.4 There are three types of GD, based on the presence and severity of neurological involvement.4 Type 1, known as the non-neuronopathic GD  characterised by haematological abnormalities such as thrombocytopenia, leukopenia and anaemia, hepatomegaly and/or splenomegaly, bone crises and/or osteoporosis, and fatigue.4  Phenotypically, there is a wide spectrum of disease manifestations, ranging from asymptomatic to severe type 1 child-onset disease.5,6 Type 2, the acute neuronopathic form, is the rarest and most severe form of GD.  It includes the rapid progression of severe neurological abnormalities early in life, leading to death in infancy or early childhood.4,6 Type 3, the chronic form, encompasses multiple phenotypes.  Type 3 typically occurs during the paediatric years and varies in severity: patients have the same symptoms as in type 1, plus some neurological involvement that generally appear later in life, such as abnormal eye movement, ataxia, seizures and dementia.4

Anaemia, thrombocytopenia, enlargement of the liver and/or spleen, and skeletal abnormalities (osteopenia, lytic lesions, pathological fractures, chronic bone pain, bone crisis, bone infarcts, osteonecrosis and skeletal deformities) are typical manifestations of type 1 GD, the most prevalent form of the disease.5 However, the severity and coexistence of different symptoms are highly variable, and GD patients are often misdiagnosed as having other malignant haematological conditions.4

Although GD is rare, clinicians are encouraged to maintain a high index of suspicion with patients presenting with atypical symptoms, and should consider testing for rare diseases where other haematological pathologies have been excluded4 or when testing for them. Such patients may be referred to a GD specialist or be tested through North West University (NWU), where global pharmaceutical company Sanofi and the NWU Centre of Human Metabolomics, headed by Prof Chris Vorster, have partnered to test for the most common lysosomal storage disorders in South Africa, including GD, using dried blood spot samples.

Says Prof. Vorster: “Rare conditions such as GD require the cooperation of a multidisciplinary team in order to find and treat them. Interventions can improve a patient’s quality of life through improvement or restoration of their physical function, so that they may carry out regular daily activities. The NWU Centre of Human Metabolomics provides internationally competitive metabolomic analytic services, and electronic results may be sent by high priority straight to healthcare practitioners, speeding up diagnosis.”

Monique Nel, Medical Advisor – Rare Diseases at Sanofi, says: “We understand the difficulty that healthcare professionals face when it comes to diagnosing patient with GD. It requires a coordinated approach to diagnosis and care for people living with the condition. Early diagnosis of GD, and the initiation of treatment will delay the occurrence of irreversible complications, and improve the patient’s quality of life. We therefore direct the attention of healthcare providers to the RD Nexus platform, which is Sanofi’s dedicated platform for rare diseases, at www.RDNexus.com. This platform offers educational materials, road maps to a differential diagnosis and how to test a patient for these conditions.”

For more information on GD and other rare diseases, visit: www.RDNexus.com

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505568/pdf/EMMM-11-e10486.pdf Accessed September 2022.
  2. Burrow TA et al. Prevalence and management of Gaucher disease. Paediatric Health, Medicine and Theraeutics 2011;2:59-73.
  3. Revel-Wilk S, et al. How we manage Gaucher Disease in the era of choices. British Journal of Haematology 2018;182:467-480.
  4. CPD Gaucher. Gaucher Disease. Medical Chronicle June 2020:30-32.
  5. Linari S, Castaman G. Clinical manifestations and management of Gaucher disease. Clinical Cases in Mineral and Bone Metabolism 2015;12(2):157-164.
  6. Roshan Lal T and Sidransky E. The spectrum of neurological manifestations associated with Gaucher Disease. Diseases 2017;5,10.
Categories : AgeingTags : Leave a comment

Why Elderly Drivers May Hit the Brake Instead of the Accelerator

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Driver at the wheel of a car
Photo by Why Kei on Unsplash

Researchers in Japan have found that older participants have longer reaction times, slower decision times, and greater brain activation in the parts of the brain involved with inhibition and switching tasks. These findings, published in the journal Brain Behavioural Research, illuminate the causes of accidents involving elderly drivers who press the brake instead of the accelerator.

With one of the oldest populations in the world, Japan is concerned about cognitive decline in drivers resulting in accidents. The police require drivers over 75 to take periodic cognitive tests. However, few studies have investigated executive functions and brain activity among older adults in terms of foot responses during braking and accelerating.

To address this gap, a group led by Professor Nobuyuki Kawai of the Graduate School of Informatics at Nagoya University in Japan scanned the brains of elderly people and students while performing pedal-pressing simulations. The researchers were particularly interested in the left dorsolateral prefrontal cortex, the part of the brain associated with inhibition and switching responses.

To simulate the response of a person’s feet and hands when driving a car, they created a new task in the laboratory called the bimanual and bipedal response selection and response-position compatibility task. During this task, a signal directed participants to press the left or right button with their left or right foot, or their left or right hand. Sometimes participants pressed the pedal in front of them, whereas at other times they had to press it diagonally. This was done to allow the researchers to assess how the participants responded in situations where the cognitive load was higher. Administering this task to both university students and elderly participants, the researchers then monitored blood flow in their brains. The results were published in Behavioural Brain Research.

They found that older participants had longer reaction times, slower decision times, and greater brain activation than younger people. Furthermore, pressing the diagonal pedal required longer reaction times and greater brain activation than pressing directly ahead in the left dorsolateral prefrontal cortex. Interestingly, this was only found when people were asked to use their feet but not their hands. In short, older people had to do more active thinking than younger people when deciding which ‘pedal’ to press with their feet.

“This indicates that the cognitive load is higher when pushing the pedal diagonally with the foot, such as when pressing the brake,” explains Professor Kawai. “When you push a diagonal pedal with your foot, you are using the frontal lobe more than when you push the pedal straight in front. In particular, the left dorsolateral frontal lobe, which is important for response switching, is more active when the foot is pressed at an angle than when the pedal is pressed straight. In these tasks, older adults have higher neural activity throughout the frontal lobe than college students.”

This study’s findings suggest that to compensate for the decline in cognitive functions, greater brain activation may be necessary in elderly people. Older people may struggle in situations with a high cognitive load, such as parking a vehicle in a narrow space. “This study suggests that the performance of older adults is vulnerable in these situations,” Professor Kawai explains. “Elderly drivers should not be overconfident that their driving is fine. Even elderly people who are normally able to drive without any problems, when a cognitive load is applied, such as when switching from one parking space to another or when talking to a passenger, things may be different and there is a chance of pressing the wrong pedal. We believe that it is important to educate elderly drivers about this fact.”

Source: Nagoya University

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Smartphones Could Serve as Pulse Oximeters in the Home

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Researchers have demonstrated that smartphones are capable of detecting blood oxygen saturation levels down to 70% – the lowest value that pulse oximeters should be able to measure, as recommended by the US Food and Drug Administration. The team published these results in npj Digital Medicine.

The technique involves participants placing their finger over the camera and flash of a smartphone, which uses a deep-learning algorithm to decipher the blood oxygen levels. When the team delivered a controlled mixture of nitrogen and oxygen to six subjects to artificially bring their blood oxygen levels down, the smartphone correctly predicted whether the subject had low blood oxygen levels 80% of the time.

“Other smartphone apps that do this were developed by asking people to hold their breath. But people get very uncomfortable and have to breathe after a minute or so, and that’s before their blood-oxygen levels have gone down far enough to represent the full range of clinically relevant data,” said co-lead author Jason Hoffman, a UW doctoral student in the Paul G. Allen School of Computer Science & Engineering. “With our test, we’re able to gather 15 minutes of data from each subject. Our data shows that smartphones could work well right in the critical threshold range.”

Another benefit of measuring blood oxygen levels on a smartphone is that almost everyone has one.

“This way you could have multiple measurements with your own device at either no cost or low cost,” said co-author Dr. Matthew Thompson, professor of family medicine in the UW School of Medicine. “In an ideal world, this information could be seamlessly transmitted to a doctor’s office. This would be really beneficial for telemedicine appointments or for triage nurses to be able to quickly determine whether patients need to go to the emergency department or if they can continue to rest at home and make an appointment with their primary care provider later.”

The team recruited six participants ranging in age from 20 to 34. Three identified as female, three identified as male. One participant identified as being African American, while the rest identified as being Caucasian.

To gather data to train and test the algorithm, the researchers had each participant wear a standard pulse oximeter on one finger and then place another finger on the same hand over a smartphone’s camera and flash. Each participant had this same set up on both hands simultaneously.

“The camera is recording a video: Every time your heart beats, fresh blood flows through the part illuminated by the flash,” said Assistant Professor Edward Wang, who started this project as a doctoral student.

“The camera records how much that blood absorbs the light from the flash in each of the three color channels it measures: red, green and blue,” said Wang, who also directs the UC San Diego DigiHealth Lab. “Then we can feed those intensity measurements into our deep-learning model.”

Each participant breathed in a controlled mixture of oxygen and nitrogen to slowly reduce oxygen levels. For all six participants, the team acquired more than 10 000 blood oxygen level readings between 61% and 100%.

The researchers used data from four of the participants to train a deep learning algorithm to extract the blood oxygen levels, and the rest of the data was used to validate the method and then test it to see how well it performed on new subjects.

“Smartphone light can get scattered by all these other components in your finger, which means there’s a lot of noise in the data that we’re looking at,” said co-lead author Varun Viswanath. “Deep learning is a really helpful technique here because it can see these really complex and nuanced features and helps you find patterns that you wouldn’t otherwise be able to see.”

The team hopes to continue this research by testing the algorithm on more people.

“One of our subjects had thick calluses on their fingers, which made it harder for our algorithm to accurately determine their blood oxygen levels,” Hoffman said. “If we were to expand this study to more subjects, we would likely see more people with calluses and more people with different skin tones. Then we could potentially have an algorithm with enough complexity to be able to better model all these differences.”

But, the researchers said, this is a good first step toward developing biomedical devices that are aided by machine learning.

“It’s so important to do a study like this,” Wang said. “Traditional medical devices go through rigorous testing. But computer science research is still just starting to dig its teeth into using machine learning for biomedical device development and we’re all still learning. By forcing ourselves to be rigorous, we’re forcing ourselves to learn how to do things right.”

Source: University of Washington