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A new technique which combines the use of two ultrasound technologies may offer an option to move kidney stones out of the ureter with minimal pain and no anesthesia, according to a new feasibility study published today in The Journal of Urology.
In the procedure, the physician uses a handheld transducer placed on the skin to direct ultrasound waves towards the stone. The ultrasound can then be used to move and reposition the stones to promote their passage, a process called ultrasound propulsion, or the break up the stone, a technique called burst wave lithotripsy (BWL).
Unlike shock wave lithotripsy, which is the standard procedure now in use and requires sedation, this technology doesn’t hurt, said lead author Dr. M. Kennedy Hall, a UW Medicine emergency medicine doctor. “It’s nearly painless, and you can do it while the patient is awake, and without sedation, which is critical.”
The research team hopes that, with this new technology, the procedure of moving or breaking up the stones could eventually be performed in a clinic or emergency room setting, Hall added.
Stones in the ureter, which leads from the kidney to the bladder, can cause severe pain and are a common reason for emergency department visits. Most patients with ureteral stones are advised to wait to see if the stone will pass on its own. However, this observation period can last for weeks, with nearly one-fourth of patients eventually requiring surgery, Hall noted.
One in 11 Americans will have a urinary stone over the course of their lifetime. The incidence appears to be increasing, according to one UW Medicine study looking at this same technology. Up to 50% of patients with a stone event will recur within five years, the study noted.

An important new clue for preventing and treating brain tumors known as gliomas has been identified in research led by the Lunenfeld-Tannenbaum Research Institute (LTRI) at Mount Sinai Hospital in Toronto and Mayo Clinic Comprehensive Cancer Center and Mayo Clinic Center for Individualized Medicine. The study, published in the journal Science, provides a rare window into the biological changes behind glioma development.
Researchers found that animal models who carry a change in DNA known as germline alteration rs55705857 developed gliomas much more frequently — and in half the time — compared to animal models without the alteration. In addition to brain tumors, the findings are relevant to other cancers and diseases.
“While we understand much of the biologic function of germline alterations within genes that code for proteins, we know very little about the biologic function of germline alterations outside of genes that code for proteins. In some way, these germline alterations interact with other mutations in cells to accelerate tumor formation,” says co-lead author Robert Jenkins, M.D., Ph.D., a genetics researcher at Mayo Clinic in Rochester. “Based on this new understanding of its mechanism of action, future research may lead to novel and specific therapies that target the rs55705857 alteration.”
The study offers new knowledge that may help clinicians determine, pre-surgery, whether a patient has a glioma.
“We expected that rs55705857 would accelerate low-grade glioma development, but we were surprised by the magnitude of that acceleration,” says co-lead author Daniel Schramek, Ph.D., a researcher at Lunenfeld-Tannenbaum Research Institute.
There are many alterations, likely thousands, outside of genes associated with the development of cancer and other diseases, but the mechanism of action is only understood for very few, Dr. Schramek says.
This study demonstrates that, with the tools of modern molecular/cell biology, it is possible to decipher much of the mechanism of action of such alterations.
Dr. Jenkins is a Ting Tsung and Wei Fong Chao Professor in Individualized Medicine Research and researcher in Mayo Clinic’s Department of Laboratory Medicine and Pathology.
Dr. Schramek is a senior investigator and holds a Kierans & Janigan Research Chair at the LTRI and is an associate professor, Department of Molecular Genetics, Faculty of Medicine, University of Toronto.
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Materials provided by Mayo Clinic. Original written by Kelley Luckstein. Note: Content may be edited for style and length.

Blocking the action of calcium signals in immune cells suppresses the most common form of asthma, but without compromising the body’s defenses against flu viruses, a new study finds.
Led by researchers at NYU Grossman School of Medicine, experiments showed that removing the gene for a calcium channel — specifically the calcium release-activated calcium (CRAC) channel made up of ORAI1 proteins — thoroughly reduced asthmatic inflammation in the lungs of mice caused by house dust mite feces, a common cause of allergic asthma. Blocking signals sent through this channel with an investigational new drug called a CRAC channel inhibitor had a similar effect.
The study revolved around the use of charged particles, mainly calcium, by human cells to send signals and flip biological switches. When triggered–whether by viral proteins or allergens — immune cells called T cells open channels in their outer membranes, letting calcium rush in to turn on signaling pathways that control cell division and secretion of cytokine molecules that help T cells communicate with other immune cells.
Past work had found that CRAC channels in T cells regulate their ability to multiply into armies of cells designed to fight infections caused by viruses and other pathogens.
Published online in Science Advances on October 7, the new study showed that the CRAC channel inhibitor reduced allergic asthma and mucus build-up in mice without sabotaging their immune system’s ability to fight influenza, a main worry of researchers seeking to tailor immune-suppressing drugs for several applications.
“Our study provides evidence that a new class of drugs that target CRAC channels can be used safely to counter allergic asthma without creating vulnerability to infections,” says senior study author Stefan Feske, MD, the Jeffrey Bergstein Professor of Medicine in the Department of Pathology at NYU Langone Health. “Systemic application of a CRAC channel blocker specifically suppressed airway inflammation in response to allergen exposure.”
About 25 million Americans suffer from asthma, with repeated episodes of wheezing, breathlessness, chest tightness, and coughing, according to the Centers for Disease Control and Prevention. The majority of those have asthma related to inhaled allergens, say the study authors.

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Amid much speculation and research about how our genetics affect the way we age, a University of California, Berkeley, study now shows that individual differences in our DNA matter less as we get older and become prone to diseases of aging, such as diabetes and cancer.
In a study of the relative effects of genetics, aging and the environment on how some 20,000 human genes are expressed, the researchers found that aging and environment are far more important than genetic variation in affecting the expression profiles of many of our genes as we get older. The level at which genes are expressed — that is, ratcheted up or down in activity — determines everything from our hormone levels and metabolism to the mobilization of enzymes that repair the body.
“How do your genetics — what you got from your sperm donor and your egg donor and your evolutionary history — influence who you are, your phenotype, such as your height, your weight, whether or not you have heart disease?” said Peter Sudmant, UC Berkeley assistant professor of integrative biology and a member of the campus’s Center for Computational Biology. “There’s been a huge amount of work done in human genetics to understand how genes are turned on and off by human genetic variation. Our project came about by asking, ‘How is that influenced by an individual’s age?’ And the first result we found was that your genetics actually matter less the older you get.”
In other words, while our individual genetic makeup can help predict gene expression when we are younger, it is less useful in predicting which genes are ramped up or down when we’re older — in this study, older than 55 years. Identical twins, for example, have the same set of genes, but as they age, their gene expression profiles diverge, meaning that twins can age much differently from each other.
The findings have implications for efforts to correlate diseases of aging with genetic variation in humans, Sudmant said. Such studies should perhaps focus less on genetic variants that impact gene expression when pursuing drug targets.
“Almost all human common diseases are diseases of aging: Alzheimer’s, cancers, heart disease, diabetes. All of these diseases increase their prevalence with age,” he said. “Massive amounts of public resources have gone into identifying genetic variants that predispose you to these diseases. What our study is showing is that, well, actually, as you get older, genes kind of matter less for your gene expression. And so, perhaps, we need to be mindful of that when we’re trying to identify the causes of these diseases of aging.”
Sudmant and his colleagues reported their results this week in the journal Nature Communications.

When struggling to conceive, every second that ticks by feels precious. That makes it easy to get discouraged: 65 percent of those who seek fertility care eventually discontinue treatment, the majority due to stress. That’s why Penn Medicine recently instituted a telemedicine-driven program aimed at seeing patients more quickly and starting treatments sooner. The program, Fast Track to Fertility, cut the time between when patients initially reached out for help to when they received their first treatment by half — getting them on the path to parenthood roughly a month and a half sooner, according to research published in NEJM Catalyst by researchers at the Perelman School of Medicine at the University of Pennsylvania.
On top of cutting the average time it took for new patients to get their first treatment (from 97 to 41 days), the program also allowed for more new patients to access fertility care, increasing the number by 24 percent in the year it was implemented as a standard of care at Penn Medicine. At a time when one in eight couples in the United States are experiencing infertility, Fast Track to Fertility allowed more than 1,000 new patients to begin treatments to help them become pregnant.
“Most of the people who seek fertility care have been trying to get pregnant for at least a year, so the emotional stakes are high and they really want to get started as soon as possible,” said the study’s senior author and Fast Track to Fertility co-founder, Anuja Dokras, MD, PhD, a professor of Obstetrics and Gynecology and chair of Gynecology for the Women’s Health Service Line. “Our findings show that this program can significantly speed up the time to treatment and, in so doing, opens the door for so many more people. These findings show this way of doings things can make real differences in people’s lives.”
Fertility care has steadily increased in demand since it was introduced, reaching a point where fertility clinics often have long waits for new patients. Fast Track to Fertility, started through the Innovation Accelerator in Penn Medicine’s Center for Health Care Innovation, seeks to speed things up by deploying a relatively small team of advanced practice providers for efficient telemedicine-based initial visits with new patients as quickly as possible. That visit also gives patients the opportunity to enroll in an artificial intelligence-guided text messaging program that helps guide them through the complex fertility “workup” swiftly and with as few hiccups as possible.
“This system has made it so that as soon as a patient contacts us, their journey begins,” said the study’s lead author and Fast Track to Fertility co-founder, Suneeta Senapati, MD,an assistant professor of Obstetrics and Gynecology. “Both partners in a couple need to complete a workup, which can include blood work, ultrasounds, X-rays, semen analysis, and more. Some parts of this are dependent on the menstrual cycle, making it a time-sensitive process, so making it as easy as possible to quickly work through — with minimal confusion — is invaluable.”
Initial pilots (which used human texters instead of artificial intelligence to test the system) reduced the wait time to new patient visits from initial contact with the practice by 88 percent, making the average wait time just four days. And no patients during those first pilots had to call the office to figure out next steps, compared to a quarter of patients who weren’t in the program.
In 2021, when the latest analysis was performed, Fast Track to Fertility was expanded to become the standard of care across Penn Medicine’s department of Obstetrics and Gynecology. In addition to halving the time to treatment and increasing new patients, they also saw appointment “no-shows” — which includes those who unexpectedly don’t go to their appointment or who need to cancel late — drop from 40 to 20 percent, a particularly important measure.
“Any time there is a no-show, we can’t backfill that appointment because of the precise timing that goes into this type of care,” Dokras said. “So any time we can reduce no-shows, that means more people can get the care they’re looking for to start their family.”
Satisfaction, both from the patients and the advanced practice providers running the system, was also found to be high. And the researchers hope that the system can be expanded to support patients throughout their fertility journey.
“These care models do not replace our clinical work force, as human interaction remains imperative to the doctor-patient relationship and care delivery. Rather, they improve efficiency — while maintaining personalized care — for both patients and their care teams to accommodate the growing demands for fertility services,” Senapati said. “In the end, this enables my colleagues and I to do more of what we got into this field for: Helping people get pregnant and bring home their babies.”

University of Maryland School of Medicine researchers have identified how multiple genes of SARS-CoV-2 affect disease severity, which could lead to new ways in how we develop future vaccines or develop newer treatments. The genes control the immune system of the host, contributing to how fiercely the body responds to a COVID-19 infection.
Although people typically think of the spike protein that forms the structural “crown” as the driving factor behind each new variant of COVID-19, research findings also show that mutations in these other “accessory” genes also play a role in how the disease progresses. Because of this, researchers believe these accessory proteins warrant further study as their mutations increasingly may become more significant as newer variants arise.
Their findings were published on August 30, 2022, in Proceedings of the National Academy of Sciences (PNAS).
The BA.4 variant of Omicron, which circulated earlier this year, was overtaken by the latest BA.5 variant of the virus circulating now. Both of these variants seem to evade the immune system due to mutations in the spike protein. Because of these spike mutations, the researchers say the previous vaccines are not as effective in preventing disease.
“What is interesting is that both BA.4 and BA.5 variants have the same genetic sequence for the spike protein,” said Matthew Frieman, PhD, Alicia and Yaya Foundation Professor of Viral Pathogen Research in The Department of Microbiology & Immunology at UMSOM. “This means it’s the other genes, the non-spike protein genes, that seem to affect the way the virus copies itself and causes disease. So, mutations in these other accessory genes are what has allowed variants like BA.5 to outcompete the earlier versions of the virus.”
The SARS-CoV-2 virus has three kinds of genes — those involved in making more copies of the virus, those that make the virus structure, and accessory genes that have other functions. For this new study, the researchers wanted to find out the function of the accessory genes. To do this, they recreated viruses missing each of four accessory proteins and then infected mice with these new viruses or the original virus. Next, they observed how each virus affected the mice.

Autonomous optimal navigation of microswimmers is in fact possible, as researchers from the Max Planck Institute for Dynamics and Self-Organization (MPI-DS) showed. In contrast to the targeted navigation of boats, the motion of swimmers at the microscale is strongly disturbed by fluctuations. The researchers now described a navigation strategy for microswimmers that does not need an external interpreter. Their findings may contribute to the understanding of transport mechanisms in the microcosm as well as to applications such as targeted drug delivery.
Whereas the shortest way between two points is a straight connection, it might not be the most efficient path to follow. Complex currents often affect the motion of microswimmers and make it difficult for them to reach their destination. At the same time, making use of these currents to navigate as fast as possible is a certain evolutionary advantage. Whereas such strategies allow biological microswimmers to better access food or escape a predator, microrobots could this way be directed to perform specific tasks.
The optimal path in a given current can readily be determined mathematically, yet fluctuations perturb the motion of microswimmers and deviate them from the optimal route. Thus, they have to readjust their motion in order to account for environmental changes. This typically requires the help of an external interpreter and takes away their autonomy.
“Thanks to evolution, some microorganisms have developed autonomous strategies that enable directed motion towards larger concentration of nutrients or light,” first author of the study Lorenzo Piro explains. Inspired by this idea, the researchers from the Department of Living Matter Physics at the MPI-DS designed strategies that allow microswimmers to navigate optimally in a nearly autonomous way.
Light as a guide for autonomous navigation
When an external interpreter defines the navigation pattern, microswimmers on average follow a well-defined path. Thus, it is a good approach to guide the microswimmer along that path within the current. This can be achieved autonomously via external stimuli, despite the presence of fluctuations. This principle could be applied to swimmers that respond to variation of light, such as certain algae, in which case the optimal path can simply be illuminated. Remarkably, the resulting performances are comparable to externally supervised navigation. “These new strategies can moreover conveniently be applied to more complex scenario such as navigation on curved surfaces or in presence of random currents,” concludes Ramin Golestanian, director at MPI-DS.
Possible applications of the study thus range from targeted drug delivery at the microscale to the optimal design of autonomous micromachines.
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Materials provided by Max Planck Institute for Dynamics and Self-Organization. Note: Content may be edited for style and length.

National Eye Institute researchers mapped the organization of human retinal cell chromatin, the fibers that package 3 billion nucleotide-long DNA molecules into compact structures that fit into chromosomes within each cell’s nucleus. The resulting comprehensive gene regulatory network provides insights into regulation of gene expression in general, and in retinal function, in both rare and common eye diseases. The study published in Nature Communications.
“This is the first detailed integration of retinal regulatory genome topology with genetic variants associated with age-related macular degeneration (AMD) and glaucoma, two leading causes of vision loss and blindness,” said the study’s lead investigator, Anand Swaroop, Ph.D., senior investigator and chief of the Neurobiology Neurodegeneration and Repair Laboratory at the NEI, part of the National Institutes of Health.
Adult human retinal cells are highly specialized sensory neurons that do not divide, and are therefore relatively stable for exploring how the chromatin’s three-dimensional structure contributes to the expression of genetic information.
Chromatin fibers package long strands of DNA, which are spooled around histone proteins and then repeatedly looped to form highly compact structures. All those loops create multiple contact points where genetic sequences that code for proteins interact with gene regulatory sequences, such as super enhancers, promoters, and transcription factors.
Such non-coding sequences were long considered “junk DNA.” But more advanced studies demonstrate ways these sequences control which genes get transcribed and when, shedding light on the specific mechanisms by which non-coding regulatory elements exert control even when their location on a DNA strand is remote from the genes they regulate.
Using deep Hi-C sequencing, a tool used for studying 3D genome organization, the researchers created a high-resolution map that included 704 million contact points within retinal cell chromatin. Maps were constructed using post-mortem retinal samples from four human donors.

When the season turns darker and colder, animals’ brown fat starts to grow. The tissue produces heat efficiently and rapidly, and regulates appetite. Brown fat is also present in people.
In a new study conducted at the Turku PET Centre, Finland, researchers observed that shorter daylight hours impact the opioid receptor signalling in the brown fat of animals. When the amount of light diminishes, the opioid receptor levels increase. The observation was done in rats living in an artificial environment imitating seasonal daylight changes.
“In the study, we observed that the number of mu-opioid receptors in brown fat was dependent on the length of daylight the rat was exposed to. This complements our previous findings that day length modulates opioid receptor levels in the brain emotional circuits in humans and rats,” says Senior Researcher Lihua Sun from the Turku PET Centre of the University of Turku.
He states that the opioid receptor activity of brown fat and brain are two separate phenomena. However, they share the same goal of helping a mammal, a person or an animal, adapt both physiologically and also emotionally to the change of seasons.
“Opioid receptor levels in the brain and brown fat might be interconnected, for example strengthening each other’s activity, but more research is needed to confirm this,” Sun emphasises.
New Conquest in Opioid Receptor Research
Professor Anne Roivainen from the Turku PET Centre tells that this is the first time mu-opioid receptor levels have been assessed in peripheral regions using positron emission tomography (PET) imaging.
“The finding highlights that mu-opioid receptors affect the seasonality of brown fat activity. Future studies should further investigate whether mu-opioid receptors in brown fat are directly related to tissue energy consumption,” says Roivainen.
Opioid receptors are parts of the cell through which the opioid hormones can impact the cell. An example of such hormones is endorphin, which promotes pleasure and relieves pain in the body.
Consequently, the functions of opioid receptors in the brain have a central role in both pain and mood and emotions. Abnormalities of receptor function have been linked to psychiatric disorders such as depression and anxiety and eating disorders. Opioid receptor levels may also be important for the seasonal affective changes such as seasonal affective disorder. Its symptoms include winter blue and overeating.
According to Roivainen and Sun, whether the seasonal variations in mu-opioid receptor levels in the brain and brown fat are underlying the seasonal affective changes still requires more scientific evidence.
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Materials provided by University of Turku. Note: Content may be edited for style and length.