Month: March 2023

Categories : Cardiovascular DiseaseTags :

Getting Under 5 Hours’ Sleep Increases Risk of Peripheral Artery Disease

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Compared with seven to eight hours, sleeping less than five hours a night is associated with a 74% raised likelihood of developing peripheral artery disease (PAD) according to a study published in the European Heart Journal – Open.

“Our study suggests that sleeping for seven to eight hours a night is a good habit for lowering the risk of PAD,” said study author Dr Shuai Yuan of the Karolinska Institute.

A Lancet study showed that more than 200 million people globally have peripheral artery disease (PAD), where arteries in the legs are clogged, restricting blood flow and increasing the risk of stroke and heart attack.

Dr Yuan said: “Insufficient night-time sleep and daytime napping have previously been associated with a raised risk of coronary artery disease which, like PAD, is caused by clogged arteries. In addition, sleeping problems are among the top ranked complaints in PAD patients. There are limited data on the impact of sleep habits on PAD and vice versa, and our study aimed to fill that gap.”

The two-part study included more than 650 000 participants. First, the researchers analysed the associations of sleep duration and daytime napping with the risk of PAD. In the second part, the investigators used genetic data to perform naturally randomised controlled trials – called Mendelian randomisation – to examine causality of the associations.

Dr Yuan said: “Observational analyses are limited by reverse causality – meaning that if an association between sleep habits and PAD is found, we cannot be certain if sleep habits caused PAD or having PAD caused the sleep habits. Mendelian randomisation is a robust method for evaluating causality and provides more certainty about the results.”

Taken together, the strongest evidence was for short sleep, where the relationship with PAD went both ways. In an observational analysis of 53 416 adults, sleeping less than five hours a night was associated with a nearly doubled risk of PAD compared with seven to eight hours (hazard ratio [HR] 1.74). This finding was supported by further analyses in 156 582 and 452 028 individuals. In the causal studies, short sleep was associated with an increased risk of PAD and, in addition, PAD was associated with an increased likelihood of short sleep. Dr Yuan said: “The results indicate that brief night-time sleep can raise the chance of developing PAD, and that having PAD increases the risk of getting insufficient sleep.”

Regarding long sleep, in an observational analysis of 53 416 adults, sleeping eight hours or more per night was linked with a 24% higher risk of PAD compared with seven to eight hours (HR 1.24). This finding was supported by analyses in two larger populations of 156 582 and 452,028 individuals. However, no causal relationships were found between long sleep and PAD. Similar results were reported for napping, where daytime nappers had a 32% higher risk of PAD compared to those who did not nap (HR 1.32) but no causal links were found. “More studies are needed on the relationships between lengthy night-time sleep, daytime napping and PAD,” said Dr Yuan. “Although we found associations in the observational studies, we could not confirm causality.”

He concluded: “More research is needed on how to interrupt the bidirectional link between short sleep and PAD. Lifestyle changes that help people get more sleep, such as being physically active, may lower the risk of developing PAD. For patients with PAD, optimising pain management could enable them to have a good night’s sleep.” 

Source: European Society of Cardiology

Categories : Cancer GenderTags :

In Women, Certain Immune Cell Hinders Pancreatic Cancer Immunotherapy

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Immunotherapy has limited effect for pancreatic cancer, and differs between men and women. A new study published in Cancer Research reveals certain immune cells in women with pancreatic cancer that, instead of fighting the tumour, interferes with the body’s immune response. These findings may pave the way for a more sex-specific treatment.

“More and more evidence is coming in that male and female hormones affect our immune system, but much remains to be done before sex can be included as a self-evident biological factor in medical research and therapy,” says the paper’s first author Fei He, former visiting researcher at Karolinska Institutet. “Our results provide new perspectives that can have high impact on the treatment of cancer.”

In recent years, immunotherapy, which stimulates the immune system to attack cancer cells, has contributed significantly to the treatment of different kinds of cancer, such as melanoma and lung, kidney and liver cancer. However, it is much less effective against pancreatic cancer, which remains one of the deadliest kinds of cancer that leaves patients, on average, with four to six months left to live after diagnosis.

Sex-biased differences in the immune response

Previous studies have shown that there are sex-bound biological differences in the male and female immune system that, amongst other effects, determine how tumours grow and the body’s ability to defend itself against them. The present study addressed what might cause such sex-related disparities in the immune response to pancreatic cancer.

The study revealed the presence of a subpopulation of myeloid cells in women that protect the tumour and prevents the immune system’s T cells from infiltrating the tumour and attacking the cancer cells.

“This sub-group of immune cells correlates with poor survival exclusively in female cancer patients,” says the study’s corresponding author and principal investigator Dhifaf Sarhan, assistant professor at the Department of Laboratory Medicine, Karolinska Institutet. “Our results show that the immune cells express a specific protein called FPR2 and can serve both as a sex-specific prognostic factor and a therapeutic target.”

New target for immunotherapy in women

The results can be useful to the development of diagnostic tools and immunotherapy for pancreatic cancer that take into account biological differences between men and women. The study used a combination of methods including single-cell RNA sequencing, proteomics, test tube and patient validation, and treatments of 3D pancreatic cancer models and mice.

“The next step is to follow up our new immunotherapy target for women,” says Dr Sarhan. “We’re also performing extensive analyses to understand how immunological sex differences drive tumour development in different ways in male and female cancer patients with the goal to find and develop immunotherapy targets for each group.”

Source: Karolinska Institutet

Categories : Cancer Diet and NutritionTags :

‘Eating the Rainbow’ Found to Reduce Prostate Cancer Risk and Improve Treatment

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New research by scientists at the University of South Australia suggests that consumption of colourful fruits and vegetables on a regular basis reduces the risk of a prostate cancer (PC) diagnosis. These foods, rich in micronutrients, also help speed up recovery from radiotherapy for the disease.

The findings, from two studies published in the journal Cancers, highlight the importance of a Mediterranean or Asian diet that includes these foods. For the first study, researchers compared micronutrient plasma concentrations of prostate cancer patients with a healthy control group, revealing low levels of lutein, lycopene, alpha-carotene, and selenium in PC patients and high levels of iron, sulphur, and calcium in the same group, relative to controls.

The second study found increased DNA damage after radiation exposure was also associated with low lycopene and selenium in blood plasma.

Men with plasma concentrations lower than 0.25ug/mL) for lycopene and/or lower than 120ug/L for selenium have an increased risk of prostate cancer and are likely to be more sensitive to the damaging effects of radiation.

Foods that are rich in lycopene include tomatoes, melons, papayas, grapes, peaches, watermelons, and cranberries. Selenium-rich foods include white meat, fish, shellfish, eggs, and nuts.

Study co-author Dr Permal Deo says that studies show that eating foods rich in lycopene and selenium is preferable to taking supplements, where the benefits are limited.

“Our recommendation is to adopt a Mediterranean diet enlisting the help of a dietician because people absorb nutrients in different ways, depending on the food, the digestive system, the person’s genotype and possibly their microbiome,” Dr Deo says.

Prostate cancer remains one of the most common and fatal cancers in men, but the nutritional deficiencies associated with it remain largely unknown, hence this study. Other risk factors, such as ethnicity, family history and age have previously been linked to prostate cancer.

“There is strong evidence that being overweight and tall increases the risk of prostate cancer. Diets high in dairy products and low in vitamin E may also increase the risk but the evidence is less clear.”

Source: University of South Australia

Categories : Diseases, Syndromes and Conditions Immune SystemTags :

Research Supports Letting A Moderate Fever Run its Course

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It may be better to let a mild fever run its course instead of automatically reaching for medication, new University of Alberta research suggests. Researchers found that, in fish models, untreated moderate fever helped them to quickly their infections, keep inflammation in check and repair damaged tissue. “We let nature do what nature does, and in this case it was very much a positive thing,” says Professor Daniel Barreda, immunologist and lead author on the study which is published in eLife.

Moderate fever is self-resolving, meaning that the body can both induce it and shut it down naturally without medication, Barreda explains. The health advantages of natural fever to humans still have to be confirmed through research, but the researchers say because the mechanisms driving and sustaining fever are shared among animals, it is reasonable to expect similar benefits are going to happen in humans.

That suggests the need to resist taking non-steroidal anti-inflammatory drugs at the first signs of a mild temperature, he says. “They take away the discomfort felt with fever, but you’re also likely giving away some of the benefits of this natural response.”

The study also sheds light on some benefits of moderate fever, which Barreda notes has been evolutionarily conserved across the animal kingdom for 550 million years. “Every animal examined has this biological response to infection.”

For the study, fish were given a bacterial infection and their behaviour was then tracked and evaluated using machine learning. Outward symptoms were similar to those seen in humans with fever, including immobility, fatigue and malaise. These were then matched to important immune mechanisms inside the animals.

The research showed that natural fever offers an integrative response that not only activates defences against infection, but also helps control it. The researchers found that fever helped to clear the fish of infection in about seven days – half the time it took for those animals not allowed to exert fever. Fever also helped to shut down inflammation and repair injured tissue.

“Our goal is to determine how to best take advantage of our medical advances while continuing to harness the benefits from natural mechanisms of immunity,” says Barreda.

Source: University of Alberta

Categories : Genetics Pain ManagementTags :

Whether Hypnosis for Pain is Effective Depends on a Patient’s Genetics

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Studies have shown that hypnosis is an effective treatment for pain for many individuals – but it depends on the patient’s susceptibility to hypnosis. Testing for hypnotisability requires special training and in-person evaluation rarely available in the clinical setting. Now, investigators have developed a fast, point-of-care molecular diagnostic test that identifies a subset of individuals. Their study, published in The Journal of Molecular Diagnostics, also found that a subset of highly hypnotisable individuals may be more likely to experience high levels of postoperative pain.

“Since hypnotisability is a stable cognitive trait with a genetic basis, our goal was to create a molecular diagnostic tool for objectively identifying individuals who would benefit from hypnosis by determining ‘treatability’ at the point-of-care,” explained co-lead investigator Dana L. Cortade, a recently graduated PhD at Stanford University. “The advancement of nonpharmacological adjuvant treatments for pain is of the utmost importance in light of the opioid epidemic.”

Prior research established that the genetic basis for hypnotisability includes four specific single-nucleotide polymorphisms (SNPs), or genetic variations, found in the catechol-o-methyltransferase (COMT) gene for a brain enzyme responsible for dopamine metabolism in the prefrontal cortex. Although SNPs can contain valuable information on disease risk and treatment response, cost, complexity and time prevent widespread use.

The investigators developed a SNP genotyping assay on a giant magnetoresistive (GMR) biosensor array to detect the optimal combination of the COMT SNPs in patient DNA samples. GMR biosensor arrays are reliable, cheaper, sensitive, and can be easily deployed in point-of-care settings using saliva or blood samples.

The study investigated the association between COMT diplotypes and hypnotisability using a clinical hypnotisability scale called the Hypnotic Induction Profile (HIP) in individuals who had participated in one of the three previous clinical trials in which an HIP was administered. An additional exploratory study of the association between perioperative pain, COMT genotypes, and HIP scores was conducted with the patients in the third cohort, who had undergone total knee arthroplasty (TKA). DNA was extracted from blood samples previously collected in the first cohort, and saliva samples were collected by mail from participants in the other two trials. Participants were considered treatable by hypnosis if they had HIP scores of 3 or higher on a scale of zero to 10.

For participants identified with the optimal COMT diplotypes by the GMR biosensor array, 89.5% scored highly on the HIP, which identified 40.5% of the treatable population. The optimal COMT group mean HIP score was significantly higher than that in the suboptimal COMT group. Interestingly, further analysis revealed that the difference was observed only in women.

“Although we had expected some difference in effect between females and males, the association between hypnotisability and COMT genotypes was strongest in the females in the cohort,” said co-lead investigator Jessie Markovits, MD, Department of Internal Medicine, Stanford School of Medicine, Stanford, CA, USA. “The difference may be due to lower numbers of males in the cohort, or because COMT is known to have interactions with oestrogen and to differ in activity by sex. Additional gene targets including COMT, with stratification by sex, could be the focus of future study.”

In the exploratory analysis of the relationship between COMT genotypes and pain after TKA surgery, the same optimal COMT individuals had significantly higher postoperative pain scores than the suboptimal group, indicating a greater need for treatment. “This supports the body of evidence that COMT genotypes impact pain, and it is also known that COMT genotypes affect opioid use after surgery. Pain researchers can use this technology to correlate genetic predisposition to pain sensitivity and opioid use with response to an evidence-based, alternative remedy: hypnosis,” Dr Cortade said.

COMT SNPs alone are not a complete biomarker for identifying all individuals who will score highly on a hypnotisability scale and experience high pain sensitivity. The GMR sensor nanoarray can accommodate up to 80 SNPs, and it is possible that other SNPs, such as those for dopamine receptors, are needed to further stratify individuals.

The investigators observe that this study highlights the utility and potential of the evolving applications of precision medicine. “It is a step towards enabling researchers and healthcare professionals to identify a subset of patients who are most likely to benefit from hypnotic analgesia,” Dr Markovits said. “Precision medicine has made great strides in identifying differences in drug metabolism that can impact medication decisions for perioperative pain. We hope to provide similar precision in offering hypnosis as an effective, non-pharmacological treatment that can improve patient comfort while reducing opioid use.”

Source: Elsevier

Categories : Metabolic Disorders PaediatricsTags :

Autism in Children Linked to Diabetes, Dyslipidaemia

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Studies have shown that children with autism spectrum disorder (ASD) have an increased risk of obesity. In turn, obesity has been linked to increased risks for diabetes, dyslipidaemia and other cardiometabolic disorders. However, the question of whether or not there is an association between autism, cardiometabolic disorders and obesity remains largely unanswered.

To help provide an insight into the possible link between ASD and cardiometabolic diseases, Texas Tech University researchers conducted a systematic review and meta-analysis. Their findings were published in JAMA Pediatrics.

In this latest meta-analysis, the researchers evaluated 34 studies that included 276 173 participants who were diagnosed with ASD and 7 733 306 who were not. The results indicated that ASD was associated with greater risks of developing diabetes overall, including both type 1 and type 2 diabetes.

The meta-analysis also determined that autism is associated with increased risks of dyslipidaemia and heart disease, though there was no significant increased risk of hypertension and stroke associated with autism. However, meta-regression analyses revealed that children with autism were at a greater associated risk of developing diabetes and hypertension when compared with adults.

Study leader Chanaka N. Kahathuduwa, MD, PhD, said the overall results demonstrate the associated increased risk of cardiometabolic diseases in ASD patients, which should prompt clinicians to more closely monitor these patients for potential contributors, including signs of cardiometabolic disease and their complications.

“We have established the associations between autism and obesity, as well as autism and cardiometabolic disease, including diabetes and dyslipidaemia,” Kahathuduwa said. “We don’t have data to support a conclusion that autism is causing these metabolic derangements, but since we know that a child with autism is more likely to develop these metabolic complications and derangements down the road, I believe physicians should evaluate children with autism more vigilantly and maybe start screening them earlier than the usual.”

Kahathuduwa also believes the study shows that physicians should think twice before prescribing medications such as olanzapine that are well known to have metabolic adverse effects to children with autism.

“Our findings should also be an eye opener for patients with autism and parents of kids with autism to simply be mindful about the higher risk of developing obesity and metabolic complications,” Kahathuduwa added. “Then they can talk with their physicians about strategies to prevent obesity and metabolic disease.”

Kahathuduwa said the next logical step for the collaborative team would be to generate evidence that either supports or rejects causality with regard to the observed associations.

Source: Texas Tech University Health Sciences Center

Categories : Medical Research & Technology Obstetrics & GynaecologyTags :

Medical Students Retain Knowledge Better from Virtual Reality Lessons

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A trial published in the International Journal of Gynecology & Obstetrics lends support to the idea that 3D virtual reality lessons can improve medical students’ retention of knowledge and understanding of complex topics in obstetrics and gynaecology.

For the study, 21 students took part in a 15-minute virtual reality learning environment (VRLE) experience on the stages of foetal development, while 20 students received a PowerPoint tutorial on the same topic, serving as a control.

While the students’ level of knowledge increased after both learning experiences, it was only retained in the VRLE group at one-week follow up. Questionnaires completed by participants reflected a high degree of satisfaction with the VRLE tool compared with the traditional tutorial.

“Virtual reality learning tools hold potential to enhance student learning and are very well received by students,” said corresponding author Fionnuala McAuliffe, MD, of University College Dublin National Maternity Hospital, in Ireland.

Source: Wiley

Categories : COVID PaediatricsTags :

Common Cold may Have Conferred COVID Immunity to Children

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Early in the COVID pandemic, it became clear that children infected with the coronavirus rarely developed serious disease. One hypothesis has been that children already have some immunity provided by memory T cells generated by common colds. Researchers at Karolinska Institutet are now able to show that OC43, one of the coronaviruses that cause common colds, boosts the immune response to COVID. The study, which is published in PNAS, could give rise to more tailored vaccine programmes for children and adults.

After studying unique blood samples from children taken before the pandemic, Karolinska Institutet researchers have now identified memory T cells that react to cells infected with SARS-CoV-2.

This new study reinforces this hypothesis and shows that T cells previously activated by the OC43 virus can cross-react against SARS-CoV-2.

Four coronaviruses cause common colds

One of the four coronaviruses causing seasonal common cold symptoms could stimulate an immune response with T cells able to also react to cells infected with SARS-CoV-2.

“These reactions are especially strong early in life and grow much weaker as we get older,” says the study’s corresponding author Annika Karlsson, research group leader at the Department of Laboratory Medicine, Karolinska Institutet. “Our findings show how the T-cell response develops and changes over time and can guide the future monitoring and development of vaccines.”

Strong immunity at the age of two

The results indicate that the memory T-cell response to coronaviruses develops as early as the age of two. The study was based on 48 blood samples from two- and six-year-old children, and 94 samples from adults between the ages of 26 and 83. The analysis also included blood samples from 58 people who had recently recovered from COVID-19.

“Next, we’d like to do analogous studies of younger and older children, teenagers and young adults to better track how the immune response to coronaviruses develops from childhood to adulthood,” says Marion Humbert, postdoctoral researcher currently at the Department of Medicine Huddinge, Karolinska Institutet, joint first author with Anna Olofsson, doctoral student at the Department of Laboratory Medicine.

Source: Karolinska Institutet

Categories : UncategorizedTags :

In Wounds, Fibroblasts also Clear Away Damaged Tissue

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Burn wounds are notoriously prone to bacterial infection and typically lead to a larger amount of scar tissue than laceration wounds, but new research shows that fibroblasts – normally considered as construction cells – clear away damaged tissue before depositing new material. The more damaged tissue there is, the longer it takes for the fibroblasts to remove the material and heal.

In APL Bioengineering, researchers from Boston University and Harvard University describe how they created a biomimetic model to study wound healing in burn and laceration wounds, which is slower in burn wound as more tissue damage is present.

Cell biologists identify four phases of wound healing: bleeding stoppage, inflammation, new tissue formation, and tissue strengthening. During the inflammation and formation stages, immune cells are thought to clear bacteria and dead cells from the wound. They also activate fibroblasts and blood vessels to begin repairs.

“Depending on the injury, the extent and duration of these four phases can wildly vary across different wound types,” said author Jeroen Eyckmans. “Given that laceration wounds are well perfused with blood, they tend to heal well. However, in burns, the blood vessels are cauterised, preventing blood from entering the wound bed and slowing down the healing process. Severe burn wounds also have large amounts of dead tissue that physically block new tissue formation.”

To study how the mode of injury impacts the healing rate of wounds, the team designed an in vitro model system made of fibroblasts embedded in a collagen hydrogel. Wounds were created in this microtissue using a microdissection knife to mimic laceration or a high-energy laser to simulate a burn.

Although both wound types were equal in size, laser ablation caused more cell death and tissue damage next to the wound margins compared to knife wounds.

“During healing, we found that the fibroblasts first cleared the damaged material from the wound before depositing new material,” said Eyckmans. “This was a surprising finding because removal of dead tissue has been attributed to specialised immune cells such as macrophages, and fibroblasts have been considered to be tissue-building cells, not tissue-removal cells.”

Given that there was more tissue damage in the laser ablation wounds, it took fibroblasts more time to remove the damage, ultimately delaying tissue healing.

Based on these findings, therapies that promote wound clearance could accelerate healing. Genetically engineered white blood cells, designed to remove dead tissue, could be particularly useful for reaching injured organs and tissues deep in the body.

Source: American Institute of Physics

Categories : Cardiovascular DiseaseTags :

Hunger Hormone Increases Cardiac Function in Heart Failure

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A clinical study published in the European Heart Journal shows that the hunger hormone ghrelin can increase the heart’s pump capacity in patients with heart failure.

Heart failure occurs when the heart muscles are weakened, such as from myocardial infarction, reducing the ability to pump blood. Current treatments can slow disease progression, but none directly increase the heart’s pumping capacity.

Ghrelin is an endogenous hormone that has many receptors distributed in cardiac muscle tissues. It increases the appetite and stimulates the release of growth hormones. The researchers believe that its receptors are a promising target for enhancing the heart’s pumping capacity.

“Heart failure is the most common cause of hospitalisation in older generations and is associated with a poor quality of life and high mortality,” says principal investigator Lars Lund, professor at the Department of Medicine, Solna, Karolinska Institutet, and senior consultant at Karolinska University Hospital. “If we can find ways to increase the heart’s pump function, we can potentially improve life quality and prognosis for these patients.”

In this double-blind study, 30 patients with heart failure at Karolinska University Hospital’s cardiology unit were randomly assigned to two groups, receiving either active treatment with ghrelin or a placebo given intravenously for two hours. The participants were followed up after two to five days.

Pump function up by 28%

After two hours’ treatment, the cardiac output had increased by an average of 28% in the ghrelin group, (4.08 ± 1.15 to 5.23 ± 1.98 L/min) compared to a small reduction in the placebo group (4.26 ± 1.23 to 4.11 ± 1.99 L/min). The increase was from more blood being pumped per beat, as the heart rate remained unchanged or was even slightly slower. At the two- to five-day follow-up, the pump capacity was still 10% higher in the ghrelin group compared to in the placebo group.

No serious adverse reactions were seen, though the ghrelin group had slightly elevated levels of a heart-failure biomarker, which would need to be investigated further. The small size of the group makes limits the generalisability of the results.

Using mouse heart cells, the researchers observed that treatment with ghrelin increased the contractile function of the heart cells, and they identified a novel molecular mechanism for this increase. The researchers now plan to do larger clinical studies.

Source: Karolinska Institutet