Publisher Health

A new review of methods to increase chances of successful conception suggests that timed intercourse using urine ovulation tests probably improves live birth and pregnancy rates in women under 40 who had been trying to conceive for less than 12 months, compared to intercourse without ovulation prediction.
The review, conducted jointly with researchers from Oxford University, the Royal Berkshire Hospital in Reading, and the Princess Anne Hospital in Southampton, included seven randomised controlled trials involving 2,464 women or couples who had been trying to conceive.
Each month there is a narrow window for successful conception due to the limited lifespan of the sperm and egg, which begins from around five days before ovulation (egg release) and lasts until several hours afterwards.
The period of a woman’s cycle can be identified by different methods, including urine ovulation tests (dipstick devices that can detect changes in hormones released into the urine, signifying when ovulation will occur), fertility awareness-based methods (FABM) (including calendar tracking, monitoring changes in cervix fluid and body temperature) or identifying when the egg is released on ultrasound. This review aimed to assess the benefits and risks of timed intercourse on pregnancy, live birth, negative effects and quality of life in couples trying to conceive.
The study found that timing intercourse around the fertile period using a urine ovulation test increased the chances of pregnancy and live birth to between 20% to 28%, compared to 18% without using urine ovulation tests. This was specifically in women under 40 trying to conceive for under 12 months.
Tatjana Gibbons, a DPhil researcher at Oxford’s Nuffield Department of Women’s & Reproductive Health and lead author on the study, said: ”Many couples find it difficult to achieve a pregnancy, which can lead to concerns about their fertility.’
‘The finding that a simple and easily available urine test can increase a couple’s chance of successful conception is quite exciting because it can empower couples with more control over their fertility journey and could potentially reduce the need for infertility investigations and treatments.’
Professor Christian M Becker of Nuffield Department of Women’s & Reproductive Health said: ‘The high threshold of evidence required in a Cochrane review makes even this moderate quality evidence for the effectiveness of urine ovulation tests quite impressive, as well as surprising considering how long they have been available for.’
However, the researchers cautioned that because many of the studies were funded by the manufacturers of the urine ovulation test, the results should be interpreted with caution.
They also found that there was insufficient evidence to conclude the effect of the other methods in the study, including timed intercourse on clinical pregnancy (ultrasound-confirmed pregnancy), the use of FABM in timed intercourse compared to intercourse without ovulation prediction.

A quarter of people are undoing the benefits of healthy meals with unhealthy snacks, which increases the risk of strokes and cardiovascular disease.
The findings, published today in the European Journal of Nutrition by researchers from the School of Life Course & Population Sciences and ZOE, details the snacking habits of 854 people from the ZOE PREDICT study.
Researchers found that half of the participants do not match the healthiness of their meals to their snacks and vice versa. This difference has a negative effect on health measures, such as blood sugar and fat levels, and addressing this could be a simple diet strategy to improve health.
Dr Sarah Berry from King’s College London and chief scientist at ZOE said: “Considering 95% of us snack, and that nearly a quarter of our calories come from snacks, swapping unhealthy snacks such as cookies, crisps and cakes to healthy snacks like fruit and nuts is a really simple way to improve your health.”
The analysis showed that the UK is a nation of snackers, with 24% of our daily energy intake from snacks such as cereal bars, pastries and fruit. The average daily snack intake in people who snack — 95% of the cohort — was 2.28 snacks a day, with 47% of people eating two snacks a day and 29% of people eating more than two.
Contrary to popular belief, the analysis showed that snacking is not unhealthy — as long as the snacks were healthy. People who ate high-quality snacks like nuts and fresh fruits frequently were more likely to have a healthy weight compared to those who don’t snack at all or those who snack on unhealthy foods. Analysis also showed good quality snacks can also result in better metabolic health and decreased hunger.
However, a quarter (26%) of the participants reported eating healthy main meals and poor-quality snacks. Poor-quality snacks, such as highly processed food and sugary treats, were associated with poorer health markers and left people feeling hungry. Unhealthy snacks were linked with higher BMI, higher visceral fat mass and higher postprandial — the period after eating a meal — triglycerides concentrations, all of which are associated with metabolic disease such as stroke, cardiovascular disease and obesity.
The most popular snacks consumed were cookies, fruit, nuts and seeds, cheese and butter, cakes and pies and granola or cereal bars. The greatest contribution to calorie intake were cakes and pies (14%), breakfast cereals (13%), ice cream and frozen dairy desserts (12%), donuts and pastries (12%), candy (11%), cookies and brownies (11%), nuts and seeds (11%).
The timing of the snacking can also be crucial to your health, as analysis showed snacking after 9pm was associated with poorer blood markers compared to all other snacking times. Snackers at this time tended to eat energy-dense foods which were high in fat and sugar.
Dr Kate Bermingham from King’s College London and senior scientist at ZOE said: “This study contributes to the existing literature that food quality is the driving factor in positive health outcomes from food. Making sure we eat a balanced diet of fruit, vegetables, protein and legumes is the best way to improve your health.”

Up to an hour after their hearts had stopped, some patients revived by cardiopulmonary resuscitation (CPR) had clear memories afterward of experiencing death and had brain patterns while unconscious linked to thought and memory, report investigators in the journal Resuscitation, published by Elsevier.
In a study led by researchers at NYU Grossman School of Medicine, in cooperation with 25 mostly US and British hospitals, some survivors of cardiac arrest described lucid death experiences that occurred while they were seemingly unconscious. Despite immediate treatment, fewer than 10% of the 567 patients studied, who received CPR in the hospital, recovered sufficiently to be discharged. Four in 10 of patients who survived, however, recalled some degree of consciousness during CPR not captured by standard measures.
The study also found that in a subset of these patients, who received brain monitoring, nearly 40% had brain activity that returned to normal, or nearly normal, from a “flatline” state, at points even an hour into CPR. As captured by EEG, a technology that records brain activity with electrodes, the patients saw spikes in the gamma, delta, theta, alpha, and beta waves associated with higher mental function.
Survivors have long reported having heightened awareness and powerful, lucid experiences, say the study authors. These have included a perception of separation from the body, observing events without pain or distress, and a meaningful evaluation of their actions and relationships. This new work found these experiences of death to be different from hallucinations, delusions, illusions, dreams, or CPR-induced consciousness.
The study authors hypothesize that the “flatlined,” dying brain removes natural inhibitory (braking) systems. These processes, known collectively as disinhibition, may open access to “new dimensions of reality,” they say, including lucid recall of all stored memories from early childhood to death, evaluated from the perspective of morality. While no one knows the evolutionary purpose of this phenomenon, it “opens the door to a systematic exploration of what happens when a person dies.”
Senior study author Sam Parnia, MD, PhD, associate professor in the Department of Medicine at NYU Langone Health and director of critical care and resuscitation research at NYU Langone, says, “Although doctors have long thought that the brain suffers permanent damage about 10 minutes after the heart stops supplying it with oxygen, our work found that the brain can show signs of electrical recovery long into ongoing CPR. This is the first large study to show that these recollections and brain wave changes may be signs of universal, shared elements of so-called near-death experiences.”
Dr. Parnia adds, “These experiences provide a glimpse into a real, yet little understood dimension of human consciousness that becomes uncovered with death. The findings may also guide the design of new ways to restart the heart or prevent brain injuries and hold implications for transplantation.”
Called the AWAreness during REsuscitation (AWARE)-II study — it followed 567 men and women who suffered cardiac arrest during hospital stays between May 2017 and March 2020 in the United States and United Kingdom. Only hospitalized patients were enrolled to standardize the CPR and resuscitation methods used, as well as recording methods for brain activity. A subset of 85 patients received brain monitoring during CPR. Additional testimony from 126 community survivors of cardiac arrest with self-reported memories was also examined to provide greater understanding of the themes related to the recalled experience of death.
The study authors conclude that research to date has neither proved nor disproved the reality or meaning of patients’ experiences and claims of awareness in relation to death. They say the recalled experience surrounding death merits further empirical investigation and plan to conduct studies that more precisely define biomarkers of clinical consciousness and that monitor the long-term psychological effects of resuscitation after cardiac arrest.

A study led by Columbia obstetricians has shown that a new intrauterine device can rapidly control postpartum hemorrhage, a major cause of severe maternal morbidity and death, in real-world situations.
“Our findings show that the device is an important new tool in managing postpartum bleeding,” says Dena Goffman, MD, professor of obstetrics and gynecology at Columbia University Vagelos College of Physicians and Surgeons and senior author of the study.
“We had previously shown that the device worked well with patients who were experiencing relatively minor bleeding, so it’s really reassuring to see that the device worked almost as well among a wider range of patients and when used by many different doctors.”
Overall, the device succeeded in controlling hemorrhage in 93% of patients who delivered vaginally and 84% who delivered by cesarean. The results were published Sept. 14 in the journal Obstetrics & Gynecology.
Postpartum hemorrhage is a major cause of severe maternal morbidity and death
Shortly after birth and delivery of the placenta, the uterus contracts and closes off the blood vessels that nourished the placenta. Failure of the uterus to contract after delivery can result in prolonged and excessive blood loss, which may necessitate blood transfusions, ICU admission, or surgery to try to stop the bleeding and, if needed, removal of the uterus.
“Less than 10% of people who give birth will have excessive postpartum bleeding, but when it happens, it can get really serious really fast,” says Goffman, who co-authored the most recent guidelines from the American College of Obstetrics and Gynecology for the treatment of postpartum hemorrhage.

Flexible thin-film electrodes placed directly on brain tissue show promise for the diagnosis and treatment of epilepsy, as demonstrated recently by scientists at Tokyo Tech. Thanks to an innovative yet straightforward design, these durable electrodes accurately match the mechanical properties of brain tissue, leading to better performance during electrocorticography recordings and targeted neural stimulation.
Measuring brain activity is a useful technique for diagnosing epilepsy and other neuropsychiatric disorders. Among the several approaches adopted, electroencephalography (EEG) is the least invasive. During EEG recordings, electrodes are typically placed on the scalp. However, this limits the resolution of EEG as the electrical signals from the brain are attenuated and distorted by the time they reach the scalp.
In contrast, electrocorticography (ECoG) involves placement of neural electrodes directly on the surface of the brain. Being in close contact with the region of interest, ECoG electrodes provide better recordings of brain activity. Moreover, it is also possible to send electrical pulses through them to stimulate specific groups of neurons with the aim of managing epileptic seizures. However, conventional ECoG electrodes have a major drawback. They usually do not match the mechanical properties and curvature of brain tissue, resulting in increased brain pressure and other adverse effects. Although soft neural electrodes have been developed to mitigate this issue, they either lack durability and strength or require complex fabrication processes.
To address these problems, a research team guided by Associate Professor Toshinori Fujie of Tokyo Institute of Technology (Tokyo Tech) has developed a new type of flexible neural electrode. Their design and findings, recently published in Advanced Materials Technologies, can revolutionize how ECoG recordings and direct neural stimulation are performed.
The substrate of the proposed electrode consists of a thin film made of a flexible material called polystyrene-block-polybutadiene-block-polystyrene (SBS). The researchers used an inkjet printer to fabricate conductive wiring on the electrode with gold nanoink. Finally, they covered the circuit by stacking another SBS layer as insulation, with laser-perforated microchannels as measurement or stimulation points.
Through extensive mechanical testing and simulations, the researchers demonstrated that the electrode accurately conforms to the shape of brain tissue containing many irregular ridges. Its straightforward design and fabrication process is a major advantage as well, since it is conducive to the widespread adoption of the proposed electrode in practical applications. “As far as we know, this is the first study to demonstrate such ultra-conformable ECoG electrodes based on printed electronics, which closely match the mechanical properties of brain tissue,” highlights Dr. Fujie.
To showcase the potential of their design, the team conducted several experiments on epilepsy rat models. Using the newly designed ECoG electrodes, they could accurately measure the neural response in the brains of these rats when one of their whiskers was mechanically stimulated. Additionally, they could visualize seizure activity during a chemically-induced epilepsy. Further, by triggering movement in the rats’ whiskers and arms via electric pulses sent through specific channels, the researchers demonstrated that the proposed electrodes can stimulate different regions of the brain.
Overall, these findings highlight the potential of flexible thin-film neural electrodes for the diagnosis and treatment of epilepsy and other brain diseases. Notably, the electrodes did not cause any inflammation or adverse effects in the rats’ brains even several weeks after the procedure, highlighting their compatibility with biological tissue.
The researchers plan on improving their design further to make it suitable for clinical applications. “The integration of our thin-film electrode with an implantable device could make it even less invasive and more sensitive to the brain’s abnormal electrical activity,” explains Dr. Fujie. “This would enable improved diagnostics and therapeutic strategies for the management of intractable epilepsy.”

New research has shown that boosting the ‘warm glow’ feeling that people experience after giving blood significantly increases repeat blood donations, which are essential for the effective running of any health service.
The research, led by the University of Nottingham shows that the positive feelings that people experience from helping others, help sustain long-term helping that is beneficial to wider society. The ideas uncovered in this research could also be applied to improve the take-up of vaccinations.
Researchers from the University of Nottingham’s School of Psychology worked with the University of Queensland and Australian Red Cross Lifeblood to refine and target messaging to blood donors and showed that reinforcing feelings of warm glow feeling following blood donation boosts repeat appointments. The results have been published today in Nature Human Behaviour.
One of the key studies in this research targeted first-time donors in Australia six weeks after their first donation and compared standard donor messaging with messages with an emphasis on the warm glow gained from donating and reinforcing the person’s identity as a blood donor.
An example message read: “We hope you’ve been basking in the warm glow that comes with donating blood, because six weeks ago as the day you became a blood donor.”
The warm-glow messaging resulted in over a 6% increase (approximately 3000 donations) in donations attributed to the warm-glow message.
Blood is an essential medicine as defined by the WHO- like antibiotics are — for the successful delivery of health care. Blood and its products are used in trauma, surgery, childbirth, to treat burns, cancer, hemophilia and other clotting disorders, sickle cell, thalassemia, palliative care, eye drop medications, and many more. This supply of blood is met by 3% of the eligible population who donate blood.

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Cancer drugs known as checkpoint blockade inhibitors have proven effective for some cancer patients. These drugs work by taking the brakes off the body’s T cell response, stimulating those immune cells to destroy tumors.
Some studies have shown that these drugs work better in patients whose tumors have a very large number of mutated proteins, which scientists believe is because those proteins offer plentiful targets for T cells to attack. However, for at least 50 percent of patients whose tumors show a high mutational burden, checkpoint blockade inhibitors don’t work at all.
A new study from MIT reveals a possible explanation for why that is. In a study of mice, the researchers found that measuring the diversity of mutations within a tumor generated much more accurate predictions of whether the treatment would succeed than measuring the overall number of mutations.
If validated in clinical trials, this information could help doctors to better determine which patients will benefit from checkpoint blockade inhibitors.
“While very powerful in the right settings, immune checkpoint therapies are not effective for all cancer patients. This work makes clear the role of genetic heterogeneity in cancer in determining the effectiveness of these treatments,” says Tyler Jacks, the David H. Koch Professor of Biology and a member of MIT’s Koch Institute for Cancer Research.
Jacks; Peter Westcott, a former MIT postdoc in the Jacks lab who is now an assistant professor at Cold Spring Harbor Laboratory; and Isidro Cortes-Ciriano, a research group leader at EMBL’s European Bioinformatics Institute (EMBL-EBI), are the senior authors of the paper, which appears today in Nature Genetics.

The fact that humans and other living organisms can develop and grow from a single cell relies on a process called embryonic development. For healthy tissue to form, cells in the embryo have to organize themselves in the right way in the right place at the right time. When this process doesn’t go right, it can result in birth defects, impaired tissue regeneration or cancer. All of which makes understanding how different cell types organize into a complex tissue architecture one of the most fundamental questions in developmental biology.
While researchers are still some distance from fully understanding the process, a group of Brown University scientists has spent the past handful of years helping the field inch closer. Their secret? A branch of mathematics called topology.
The research team at Brown, made up of biomedical engineers and applied mathematicians, created a machine learning algorithm using computational topology that profiles shapes and spatial patterns in embryos to study how these cells organize themselves into tissue-like architectures. In a new study, they take that system to the next level, opening a path to studying how multiple types of cells assemble themselves.
The work is described in npj Systems Biology and Applications.
“In tissues, there may be differences in how one cell adheres to the same cell type, relative to how it adheres to a different cell type,” said Ian Y. Wong, an associate professor in Brown’s School of Engineering who helped develop the algorithm. “There’s this interesting question of how these cells know exactly where to end up within a given tissue, which is often spatially compartmentalized into distinct regions.”
For example, in an animal embryo, the outer layer of cells goes on to form skin, the middle layer forms muscle and bone, while the innermost layer forms the liver or lungs. Cells within each layer will preferentially adhere to each other, sorting apart from cells in other layers that go on to form other parts of the body.
In the 1970s, scientists discovered that cells within frog embryos could be gently separated apart and when they were mixed back together, they would spontaneously rearrange into their initial organization. This occurs because the cells have different affinities for each other, and as they assemble and cluster, certain topological patterns of linkages and loops are preserved.

Constant exposure of cells to stressing agents, such as pathogens, may disturb an organism’s normal functioning. To fight stress, cells have developed several coping mechanisms, including the inflammatory response.
While inflammation is necessary, too much of it can impair cell and organ function. This is the case with cytokine storms — inflammatory cascades during an infection that can spiral out of control and lead to severe disease and even death, as recently highlighted during the COVID-19 pandemic.
In a new paper published in Science, EMBL Grenoble and University of Geneva researchers provide essential insights on a protein called p38?, belonging to the Mitogen Activated Protein Kinase (MAPK) family, which is an important cellular ‘switch’ triggering the inflammatory response. They have obtained the first structure of p38? being activated by another regulatory protein kinase — MKK6 — opening up new directions to develop drugs to stop cytokine storms.
The final switch: a drug target
Matthew Bowler, a researcher at EMBL Grenoble, has been studying kinases for more than a decade. This group of enzymes plays an important role in regulating complex processes in the cell by acting as a ‘switch’ to transmit signals and activate gene expression. They do so by phosphorylation — adding a chemical group, phosphate, to other molecules to modulate their function.
Bowler’s work particularly focuses on MAP kinases, key players involved in the inflammatory response. Inflammation is switched on via a series of kinases, which activate each other in a cascade of reactions, the final kinase in the series being responsible for activating gene transcription required for inflammation. This process releases cytokines, pro-inflammatory signalling molecules, which, in case of overactivation, can lead to cytokine storms.
This kinase chain reaction is well regulated and is similar to a logic circuit: the inflammation response requires specific buttons to be switched on, ultimately activating p38? — the meeting point where all the signals converge and the last switch of the inflammatory process.

Researchers at the Francis Crick Institute, King’s College London and Guy’s and St Thomas’ NHS Foundation Trust have characterised a specialised type of immune cell, which plays a key role in protecting and repairing the cells in the healthy human gut.
These protective immune cells are depleted in inflammatory bowel disease (IBD), leaving patients vulnerable to disease progression and severe complications. The findings could lead to better clinical management and treatment options for people living with these conditions.
IBD is the collective term for Crohn’s disease and ulcerative colitis, two currently incurable conditions which involve excessive inflammation in the gut, causing debilitating symptoms like pain and diarrhea. IBD is common, affecting 1 in 125 people in the UK, and its incidence is growing globally. Often starting in childhood and early adult life, it impacts some of the most socially and economically important periods of a person’s life.
As part of their study, published today in Science, the researchers investigated tissue from over 150 patients at Guy’s and St Thomas’ NHS Foundation Trust, dissecting a major population of T cells called gamma delta (γδ) T cells in the colons of people with healthy guts and people with IBD. In healthy guts, there was a unique specialised subset of gamma delta cells, termed V-gamma-4 (Vg4) cells, that intriguingly were significantly altered and often conspicuously depleted in inflamed IBD samples.
Prior to this work, the team at the Crick and King’s had identified molecules in the healthy gut epithelium (the cells lining the gut walls) which directly interact with Vg4 T cells. So, in this new study they tested whether losing this normal interaction between Vg4 T cells and the epithelium was underpinning disease.
To do this, the team looked at relatively rare individuals carrying a gene that severely limits this interaction, and found that whereas carrying this gene didn’t increase the chance of developing IBD, for those who already developed Crohn’s Disease, it significantly increased the risk of disease progression and the development of severe complications.
The researchers also observed that, in people whose inflammation had improved, those with restored Vg4 T cell function were less likely to relapse than those who did not. This suggests that assessing the status of Vg4 T cells could be a useful biomarker for disease progression.