Scientists discover secret to waking up alert and refreshed

Do you feel groggy until you’ve had your morning coffee? Do you battle sleepiness throughout the workday?
You’re not alone. Many people struggle with morning alertness, but a new study demonstrates that awaking refreshed each day is not just something a lucky few are born with. Scientists at the University of California, Berkeley, have discovered that you can wake up each morning without feeling sluggish by paying attention to three key factors: sleep, exercise and breakfast.
The findings come from a detailed analysis of the behavior of 833 people who, over a two-week period, were given a variety of breakfast meals; wore wristwatches to record their physical activity and sleep quantity, quality, timing and regularity; kept diaries of their food intake; and recorded their alertness levels from the moment they woke up and throughout the day. Twins — identical and fraternal — were included in the study to disentangle the influence of genes from environment and behavior.
The researchers found that the secret to alertness is a three-part prescription requiring substantial exercise the previous day, sleeping longer and later into the morning, and eating a breakfast high in complex carbohydrates, with limited sugar. The researchers also discovered that a healthy controlled blood glucose response after eating breakfast is key to waking up more effectively.
“All of these have a unique and independent effect,” said UC Berkeley postdoctoral fellow Raphael Vallat, first author of the study. “If you sleep longer or later, you’re going to see an increase in your alertness. If you do more physical activity on the day before, you’re going to see an increase. You can see improvements with each and every one of these factors.”
Morning grogginess is more than just an annoyance. It has major societal consequences: Many auto accidents, job injuries and large-scale disasters are caused by people who cannot shake off sleepiness. The Exxon Valdez oil spill in Alaska, the Three Mile Island nuclear meltdown in Pennsylvania and an even worse nuclear accident in Chernobyl, Ukraine, are well-known examples.

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How immune cells prevent cognitive decline

Could the underproduction of poorly understood immune cells contribute to Alzheimer’s disease and other forms of cognitive decline? A Rutgers study in Nature Immunology suggests it may — and that increasing these cells could reverse the damage.
Rutgers researchers deactivated the gene that produces mucosal-associated invariant T cells (MAITs) in mice and compared the cognitive function of normal and MAIT cell-deficient mice. Initially, the two groups performed identically, but as the mice grew into middle age, the genetically altered mice struggled to form new memories.
Researchers then injected the genetically altered mice with MAITs, and their performance in learning and memory-intensive tasks such as swimming through a water maze returned to normal.
The study authors believe this is the first work to link MAITs to cognitive function and hope to follow it up with research that compares MAIT numbers in healthy humans and those with cognitive diseases such as Alzheimer’s.
“The MAIT cells that protect the brain are located in the meninges, but they are also present in blood, so a simple blood test should let us compare levels in healthy subjects and those with Alzheimer’s disease and other cognitive disorders,” said Qi Yang, senior author of the study and associate professor at the Child Health Institute of New Jersey at Rutgers Robert Wood Johnson Medical School.
MAIT cells, which were discovered in the 1990s, were already known to be the most abundant innate-like T cells in humans and to be particularly numerous in the liver and skin. The Rutgers study was the first to detect these cells, which are not fully understood when it comes to fighting disease, in the meninges, the membrane layers that cover the brain.
MAITs nested in the meninges appear to protect against cognitive decline by creating antioxidant molecules that combat toxic byproducts of energy production called reactive oxidative species. Without MAITs, the reactive oxidative species accumulate in the meninges and cause meningeal barrier leakage. When the meningeal barrier leaks, potentially toxic substances enter and inflame the brain. This accumulation eventually disrupts brain and cognitive function.
Genetic alteration prevented the experimental mice from producing any MAIT cells, but humans can probably increase MAIT cell production by altering their diets or making other lifestyle changes, said Yuanyue Zhang, the lead author of the study and a postdoctoral researcher at the Child Health Institute of New Jersey.
“MAIT cell production is connected to the bacteria in your gut microbiome,” Zhang said. “People who grew up in relatively sterile environments or took antibiotics frequently make fewer of them than people who grew up in more rural areas, where there is more exposure to beneficial bacteria. But everyone may improve their microbiota by changing their diet or living environment. This is just one more reason to pursue a natural and healthy lifestyle.”
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Materials provided by Rutgers University. Original written by Andrew Smith. Note: Content may be edited for style and length.

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Retinal cells may have the potential to protect themselves from diabetic retinopathy

About one third of patients with diabetes mellitus (DM) develop diabetic retinopathy (DR), a leading cause of blindness in working-age individuals. DR typically develops after many years of DM, and some patients do not develop DR for more than 50 years. New research suggests that an endogenous system that protects human retinal endothelial cells from harmful effects of the hyperglycemia (an excess of blood sugar) may be responsible for the delayed onset of DR. Furthermore, degradation of this protective system over time may set the stage for development of DR. The new study appears in The American Journal of Pathology, published by Elsevier.
“The prevailing understanding of what causes DR predicts that it will develop soon after the onset of DM,” explained lead investigator Andrius Kazlauskas, PhD, Departments of Ophthalmology and Visual Sciences and Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA. “Yet this is not the case. Although the long delay from the onset of DM to the development of DR is a well-known clinical phenomenon, there is relatively little effort to investigate the underlying reason for this delay. Uncovering this information constitutes an exciting opportunity to improve current approaches to prevent DM from progressing to DR.”
Exposing cultured cells, such as vascular endothelial cells, to high glucose is a common in vitro model of DR. The investigators cultured human retinal endothelial cells in either normal glucose or high glucose-containing media. Unexpectedly, they found that prolonged exposure to high glucose was beneficial, not detrimental. After one day, the health of the cells declined, but as the duration of exposure was prolonged, the cells recovered and acquired resistance to DM-related damage such as inflammation and death.
The investigators found that the adaptation was associated with improved mitochondria functionality. Mitophagy is the process in which cells remove damaged mitochondria, and disruption of this intrinsic quality control system is associated with many diseases. Though initially compromised, mitochondrial functionality was improved after 10 days of exposure to high glucose, with increased clearance of damaged mitochondria. Interfering with the mitochondrial dynamics compromised the cells’ ability to endure high glucose. Susceptibility to cell death increased, and responsiveness of vascular endothelial growth factor deteriorated.
Dr. Kazlauskas said these observations indicate the existence of an endogenous system that protects human retinal endothelial cells from the deleterious effects of hyperglycemia. “The compelling role of mitochondrial dysfunction in the development of DR supports our central concept of a hyperglycemia-induced mitochondrial adaptation (HIMA) system, the purpose of which is to preserve the functionality of mitochondria. We posit that the loss of HIMA sets the stage for advancing to DR.”
An important component of the HIMA concept is that improving the functionality of a subset of retinal cells will be beneficial for the whole retina. Previous research has found even a small reduction in degree or type of insult to the retina can protect animals that have DM from developing DR. Together these discoveries suggest that the development of DR involves a relatively small shift in the balance between exogenous insults and the endogenous systems that prevent DM-driven damage and drivers of pathogenesis.
Dr. Kazlauskas observed that the increasing incidence of DM, and consequently of DR, around the world exacerbates the need for effective approaches to protect patients from this serious complication. “Does HIMA exist in vivo, does it protect patients from DR, and is its demise a prerequisite for progression to DR? Our ongoing research is focused on answering these open questions,” he concluded.
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Materials provided by Elsevier. Note: Content may be edited for style and length.

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Machine learning model builds on imaging methods to better detect ovarian lesions

Although ovarian cancer is the deadliest type of cancer for women, only about 20% of cases are found at an early stage, as there are no real screening tests for them and few symptoms to prompt them. Additionally, ovarian lesions are difficult to diagnose accurately — so difficult, in fact that there is no sign of cancer in more than 80% of women who undergo surgery to have lesions removed and tested.
Quing Zhu, the Edwin H. Murty Professor of Biomedical Engineering at Washington University in St. Louis’ McKelvey School of Engineering, and members of her lab have applied a variety of imaging methods to diagnose ovarian cancer more accurately. Now, they have developed a new machine learning fusion model that takes advantage of existing ultrasound features of ovarian lesions to train the model to recognize whether a lesion is benign or cancerous from reconstructed images taken with photoacoustic tomography. Machine learning traditionally has been focused on single modality data. Recent findings have shown that multi-modality machine learning is more robust in its performance over unimodality methods. In a pilot study of 35 patients with more than 600 regions of interest, the model’s accuracy was 90%.
It is the first study using ultrasound to enhance the machine learning performance of photoacoustic tomography reconstruction for cancer diagnosis. Results of the research were published in the December issue of the journal Photoacoustics.
“Existing modalities are mainly based on the size and shape of the ovarian lesions, which do not provide an accurate diagnosis for earlier ovarian cancer and for risk assessment of large adnexal/ovarian lesions,” said Zhu, also a professor of radiology at the School of Medicine. “Photoacoustic imaging adds more functional information about vascular contrast from hemoglobin concentration and blood oxygen saturation.”
Yun Zou, a doctoral student in Zhu’s lab, developed a new machine learning fusion model by combining an ultrasound neural network with a photoacoustic tomography neural network to perform ovarian lesion diagnosis. Cancerous lesions of the ovaries can present in several different morphologies from ultrasound: some are solid, and others have papillary projects inside cystic lesions, making them more difficult to diagnose. To improve overall diagnosis of ultrasound, they added the total hemoglobin concentration and blood oxygenation saturation from photoacoustic imaging, both of which are biomarkers for cancerous ovarian tissue.
“Our results showed that the ultrasound-enhanced photoacoustic imaging fusion model reconstructed the target’s total hemoglobin and blood oxygen saturation maps more accurately than other methods and provided an improved diagnosis of ovarian cancers from benign lesions,” Zou said.
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Materials provided by Washington University in St. Louis. Original written by Beth Miller. Note: Content may be edited for style and length.

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New method of spinal cord tissue repair

A unique new material developed at University of Limerick in Ireland has shown significant promise in the treatment of spinal cord injury.
The research conducted at UL’s Bernal Institute — published in the journal Biomaterials Research — has made exciting progress in the field of spinal cord tissue repair.
New hybrid biomaterials developed at UL in the form of nanoparticles and building on existing practice in the tissue engineering field, were successfully synthesised to promote repair and regeneration following spinal cord injury, according to the researchers.
The UL team led by Professor Maurice N Collins, Associate Professor, School of Engineering at UL and lead author Aleksandra Serafin, a PhD candidate at UL, used a new kind of scaffolding material and a unique new electrically conducting polymer composite to promote new tissue growth and generation that could advance the treatment of spinal cord injury.
“Spinal Cord Injury remains one of the most debilitating traumatic injuries a person can sustain during their lifetime, affecting every aspect of the person’s life,” explained Professor Collins.
“The debilitating disorder results in paralysis below the level of injury and, in the US alone, the annual healthcare costs for SCI patient care are $9.7 billion. As there is currently no widely available treatment, continuous research into this field is crucial to find a treatment to improve the patient’s quality of life, with the research field turning towards tissue engineering for novel treatment strategies.

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NYC Will Hospitalize Mentally Ill People Involuntarily

Mayor Eric Adams directed the police and emergency medical workers to hospitalize people who appear to be severely mentally ill, even if they pose no threat to others.Mayor Eric Adams announced a major effort on Tuesday to remove people with severe, untreated mental illness from the city’s streets and subways, saying New York had “a moral obligation” to address “a crisis we see all around us.”The effort will involve hospitalizing people involuntarily, even if they do not pose an immediate risk of harm to others.“The common misunderstanding persists that we cannot provide involuntary assistance unless the person is violent,” Mr. Adams said. “This myth must be put to rest. Going forward, we will make every effort to assist those who are suffering from mental illness and whose illness is endangering them by preventing them from meeting their basic human needs.”The city said it would roll out training immediately to police officers, Emergency Medical Services staff and other medical personnel to “ensure compassionate care.” But the city’s new directive on the policy acknowledges that “case law does not provide extensive guidance regarding removals for mental health evaluations based on short interactions in the field.”Frequently, homeless people with severe mental illness are brought to hospitals, only to be discharged a few days later when their conditions improve slightly. Mr. Adams said the city would direct hospitals to keep those patients until they are stable and to discharge them only when there is a workable plan in place to connect them to ongoing care.Hospitals often cite a shortage of psychiatric beds as the reason for discharging patients, but the mayor said that the city would make sure there were enough beds for people who are removed. He noted that Gov. Kathy Hochul had agreed to add 50 new psychiatric beds. “We are going to find a bed for everyone,” Mr. Adams said.

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Hunting brain cancer cells

Understanding how cancer cells evolve from healthy brain cells and evade treatment could open up potential new drug therapies for glioblastomas, one of the most common and lethal brain cancers, new research has revealed.
By bringing together neuroscience and oncology, the team from Flinders University and the South Australian Health and Medical Research Institute (SAHMRI) is hopeful of finding a new method to treat the deadly disease.
“Glioblastomas can affect anyone and only 5% of patients survive more than 5 years following their diagnosis,” says study senior author Associate Professor Cedric Bardy from Flinders University and Group Leader of SAHMRI’s Laboratory for Human Neurophysiology and Genetics.
“A major therapeutic challenge is the variability and adaptability of these brain tumour cells. From patient to patient, glioblastoma tumours are composed of several types of cells in varying proportions. It’s these variations and their incredible capacity to quickly change their identity to hide and escape treatments that make them challenging to eradicate.”
“However, recent advances in genetics have shown that the cell types found within glioblastomas maintain some resemblance to the cells of origin, before they became cancerous, and use molecular pathways common with brain cells for growth and survival or when changing their identity.”
In a new study, published in Trends in Cancer, the team explore these similarities and differences in a bid to shed light on the potential pathways used by tumour cells to escape treatment.

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For memory formation, organization matters

Although we know that groups of cells working together in a specific brain region — the hippocampus — are vital for making, storing, and retrieving many types of memories, we still don’t have a clear idea of how these cells are organized. Researchers in Japan have recently identified an important piece of this puzzle; in rats, fear-based memories were made when cells in the hippocampus formed discrete clusters, suggesting that memory formation requires cells to be organized in a specific arrangement. The research also indicates that sleep is important for the stability of these cell clusters.
Most previous studies looking at the cellular organization of memories have used a technique called electrophysiology, which is based on brain activity that brain cells use to talk to one another. A major limitation of this technique is that it only allows the examination of a relatively small number of cells at a time, and within a limited area. Researchers from the University of Tsukuba used a different approach.
“A technique called ‘immediate early gene imaging’ allowed us to visualize cells that were active at a specific time within the entire rat hippocampus, rather than just a small part of it,” explains Dr. Jiyeon Cho, lead author of the study. “We were able to see that, when memories were being formed, groups of active cells were organized in small, compact clusters throughout the hippocampus.”
The researchers had previously used the same technique to identify similar small clusters of active cells during the formation of two other kinds of hippocampal-dependent memory. Together, their findings suggest that memory-encoding cells in the hippocampus need to be organized in a certain way in order to form memories.
Because sleep is vital for memory formation, the research team then decided to examine whether sleep had any effects on cluster organization. When rats were allowed to sleep after being trained to remember a fear-inducing stimulus (a small electric shock to the paws), they had much stronger memories of the fear, and there was also more clusters of active cells in their hippocampi.
“Together, our results demonstrate that the organization of cell clusters in the hippocampus is important for memory formation, and suggest that sleep helps to stabilize cell clusters to improve memory,” says senior author of the study Professor Constantine Pavlides. “These findings take us one step closer to understanding exactly how memory works.” A better understanding of memory at a cellular level and how the network in the brain works together to perform memory may help us to improve the quality of life one day of millions of people living with dementia and other memory-related disorders, which are currently very difficult to treat.
This research was supported by JSPS KAKENHI grant number 15K13157, 18K03168 and 26285161 to Professor Pavlides; Dr. Cho was a recipient of the Otsuka Toshimi Scholarship Foundation.
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Materials provided by University of Tsukuba. Note: Content may be edited for style and length.

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New target in the fight against heart disease

Soon after cholesterol and fat start depositing on the lining of the blood vessels that supply your heart, the smooth muscle cells that give the blood vessels strength and flexibility start to get bigger and multiply.
While scientists studying the phenomenon suspect these vascular smooth muscle cells are trying to help, this atypical behavior for these strong cells instead contributes to coronary artery disease, the most common type of heart disease in the United States.
In a bit of a vicious cycle, stents as well as bypass grafts used to treat coronary artery disease can prompt the same response.
Now Medical College of Georgia scientists report new insight into how the cells enable this unhealthy growth and a new target to intervene.
The endothelial cells that line our blood vessels are in constant communication with the layers of vascular smooth muscle cells that encase them and play a key role in regulating our blood pressure, says Yuqing Huo, MD, PhD and director of the Vascular Inflammation Program in the Vascular Biology Center at MCG.
In states of good health, for example, the two cell types share messages about how it’s time for our blood vessels to dilate a little because we are exercising. Early in vascular disease, however the conversations change, says Huo, corresponding author of the study in the American Heart Association journal Circulation.

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Pregnant women's cannabis usage in legalized U.S. states raises calls for screening

Pregnant women living in US states where cannabis is legal must be screened for the drug, for the health of both mother and baby, claim scientists who in a new national study have found that they are far more likely to use the substance.
Published in The American Journal of Drug and Alcohol Abuse, the peer-reviewed research shows pregnant women were around 4.6 times more likely to report using cannabis, where it is legal for medical and recreation, compared to where CBD is only allowed.
A large proportion of women reported using the drug for medical purposes, which is in keeping with “a growing body of evidence” that suggests in order to alleviate pregnancy symptoms cannabis is being used as a substitute for medical drugs in legalized areas.
“Therefore it is increasingly important to evaluate the risk-benefit profile of cannabis as compared to other medical treatments to understand any potential therapeutic indications for cannabis use in pregnancy,” says Lead Author Kathak Vachhani, who was a student in the Keenan Research Summer Student Program at St. Michael’s Hospital, a site of Unity Health Toronto, when the research was conducted.
The team is calling for prenatal and primary care providers to screen and counsel patients regarding cannabis use in pregnancy, particularly in states where it is legal, for the potential effects on fetal development.
They also state public messaging “around the risks” of cannabis in pregnancy is “particularly relevant now,” as many states have recently implemented cannabis laws and established cannabis markets.

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