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  • Novel Plant-Derived Compound May Be Game-Changer for Drug-Resistant Tuberculosis

    A plant-derived compound was shown in a recent study to kill strains of tuberculosis that were resistant to existing therapies.

    The compound was found in a plant native to North America, and was not only able to suppress dormant TB bacteria from resurfacing but also didn’t damage the gut microbiome.

    Tuberculosis is the second-leading killer of humans from an infectious disease worldwide, and has been developing resistance to many of the antibiotics previously used to treat it.

    Caused by a species of bacteria that invades the respiratory system called Mycobacterium tuberculosis, it can also affect the heart, brain, and spinal column.

    A new study published in the journal Anti-inflammatory Nutraceuticals and Chronic Diseases, found that sanguinarine, a derivative of bloodroot, a wildflower found in North America, could combat multidrug-resistant tuberculosis (MRTB) after being genetically modified to reduce its natural toxicity.

    TB is treated with multiple medications over a 6-month period, exposing the human organism to substantial weakening. By contrast, the sanguinarine selectively targeted the bacteria responsible for MRTB, leaving harmless and beneficial bacteria intact.

    However, in its natural form, sanguinarine is toxic to human cells, so Dr. Jim Sun, senior author and assistant professor at the University of British Columbia’s Department of Microbiology and Immunology, led a team to genetically reduce the toxicity of the phytochemical while increasing its potency as a tuberculosis killer.
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    • Impressive breakthrough

      First Patient to Have Brain Tumor Removed Through Her Eyebrow Leaves Hospital in 2 Days Thanks to Technique

      A 75-year-old woman has become the first person in the world to have a brain tumor removed through an eyebrow incision, according to the UK’s National Health Service (NHS).

      The new procedure not only slashes the hours needed on the operating table, but patient recovery time, as well.

      Doreen Adams underwent the unique procedure after a previous craniotomy to remove the tumor produced an unsuccessful result.

      “The difference in the two surgeries is night and day,” reported Adams, who was able to leave the hospital in Scotland two days after the surgery.

      The operation was carried out by pioneering NHS surgeon Anastasios Giamouriadis in Grampian, Scotland. He adapted an already existing technique and used it to remove tumor growth, a surgery that leaves patients with only a small scar and a temporary black eye.

      The procedure also allows for surgeons to carry out the operation more quickly than a traditional craniotomy, which removes parts of the skull to expose the brain. The new method takes just three hours, compared to the craniotomy’s required 8-10.

      “The recovery after the craniotomy was tough. It took a lot of time,” said the Aberdeen woman who was refereed to Dr. Giamouriadis after the surgery unfortunately did not solve the problem.

      In contrast, her recovery following the surgery at ARI (the main teaching hospital in Grampian associated with the University of Aberdeen) was “much, much quicker”.

      “I was out of hospital two days later and back to my normal life almost immediately.”
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      • Type 2 Diabetes Patients Who Stick to Low-Carb Diet May Be Able to Stop Taking Medication: Study

        People with type 2 diabetes who stick to a low-carb diet may be able to stop taking medication, suggests a new study.

        American researchers found low-carbohydrate diets may improve the beta-cell function in patients being treated for the condition, which affects around 34 million Americans and one in 15 people worldwide.

        Type 2 diabetes most often develops in people aged 45 or older, but more and more children, teens and young adults are also developing the disease.

        The researchers explained that beta-cells are endocrine cells in the pancreas that produce and release insulin, the hormone that controls blood sugar levels.

        People with the disease have a compromised beta-cell response to blood sugar, possibly due in part to eating too many carbs. ‘Empty carbs’ are full of sugar and white flour, which have a high glycemic index, which means they cause blood sugar and insulin levels to spike rapidly after eating.

        They include refined grains that have been stripped of bran, fiber, and nutrients, such as white bread or bagels, pizza dough, chips, pasta, pastries, white rice, sweet desserts, and many breakfast cereals.
        Interesting
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        • As someone who often struggles to get a good nights sleep, this is intriguing.

          Device from MIT Startup Helps People Fall Asleep - Putting Your Mind on 'Do Not Disturb'

          A team of MIT graduates has invented a commercial device that will give an alternative to sleeping pills for those who struggle to sleep.

          It’s a minimally disruptive headband that looks like something that would be sold at an Apple Store. Technically speaking it’s an electroencephalogram (EEG) that sends audio waves into the brain to better align the brain regions to help the onset of sleep.

          In a small study of the effects of the EEG headband, called Elemind, individuals with sleep-onset insomnia were able to fall asleep 10 to 15 minutes faster when wearing the Elemind.

          Elemind was founded by David Wang and Ed Boyden—both graduates of MIT, and along with helping people who have trouble sleeping, the method may also be effective for slowing or preventing cognitive decline.

          “We wanted to create a nonchemical option for people who wanted to get great sleep without side effects, so you could get all the benefits of natural sleep without the risks,” says Meredith Perry, Elemind’s CEO.

          “There’s a number of people that we think would benefit from this device, whether you’re a breastfeeding mom that might not want to take a sleep drug, somebody traveling across time zones that wants to fight jet lag, or someone that simply wants to improve your next-day performance and feel like you have more control over your sleep.”

          The founding scientists got their start using transcranial electric stimulation to try and moderate essential tremor syndrome but later moved to a less-regulated, less-explored field: sleep.
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          • Study Raises Hopes of Treating Aggressive Cancers by Identifying Fragments of Rogue DNA

            A breakthrough in understanding how and why some cancer tumors are particularly aggressive and non-responsive to treatments has placed blame on breakaway strands of roguish DNA.

            The discovery implicates several documented forms of cancer, including of the breasts, lungs, and brain, and also offered hope for identifying and treating these tumors in future patients.

            The center of the discovery is something called extrachromosomal (external from the chromosome) DNA, or ecDNA for short. Sequences of our genetic coding are wrapped tightly around histones with the help of 23 pairs of chromosomes. This keeps the code small enough to fit inside a cell nucleus.

            In some cases, DNA can break off the chromosomes and sit apart inside the nucleus, a rare occurrence that was once considered insignificant in the development of cancer. However, in a series of three papers published by a coalition of US-UK researchers, these bits of ecDNA were found to be present in tumor cells of some of the most aggressive and treatment-resistant cancers.

            “This is not just a discovery about what can make cancer so bad, it is actually pointing the way to a new set of therapies,” said Paul Mischel, a professor of pathology at Stanford University, author of one of the three papers, and director of the lab in which all three were conducted.

            “There’s a path forward for developing new treatments because this type of DNA is different and it creates vulnerabilities that are different,” he told the Guardian.

            The ecDNA fragments, found in 17.1% of all tumors examined in the studies, carried cancer-driving genes and other genes that suppress the immune system. The studies also found that ecDNA can replicate—chaotically—and that this also drives cancer growth.
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            • Hope for Patients with Aggressive Breast Cancer: Vaccine Trial Results in 88% Survival Rate After 3 Years

              Breast cancer patients have been given fresh hope after a new vaccine showed “promise” in treating an aggressive form of the disease.

              The results came in a clinical trial involving American patients with triple-negative breast cancer who received an experimental drug designed to prevent the recurrence of tumors.

              The trial, using a therapy designed by researchers at Washington University School of Medicine in St. Louis, is the first to report results for a “neoantigen DNA vaccine” for breast cancer patients.

              The findings, published in the journal Genome Medicine, showed the vaccine to be “well-tolerated” and to properly stimulate the immune system.

              The trial involved 18 patients diagnosed with a yet-to-metastasize triple-negative breast cancer. Each patient received the standard of care and three doses of a personalized vaccine tailored to target key mutations in their specific tumor and train immune cells to recognize and attack any cells bearing the mutations.

              Following treatment, 14 of the 18 patients showed immune responses to the vaccine and, after three years, 16 patients remained cancer-free.

              While the early-stage trial was designed to evaluate the safety of the vaccine and did not include a control group to determine efficacy, the research team analyzed historical data from patients with triple-negative breast cancer treated with the standard of care only.

              In that group, on average, only about half of patients remained cancer-free three years after treatment.

              Study senior author Professor William Gillanders, of Washington University School of Medicine, admits it’s not a perfect comparison, and says there are key limitations of this type of analysis.

              ​“But we are continuing to pursue this vaccine strategy and have ongoing randomized controlled trials that do make a direct comparison between the standard of care plus a vaccine, versus standard of care alone,” he said.

              “We are encouraged by what we’re seeing with these patients so far.”
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              • In10 Seconds, an AI Model Detects Cancerous Brain Tumors Often Missed During Surgery

                Researchers have developed an AI-powered model that can determine in 10 seconds during surgery if any part of a cancerous brain tumor that could be removed remains.

                The technology, called FastGlioma, outperformed conventional methods for identifying what remains of a tumor by a wide margin, according to the research team led by the universities of Michigan and California and the paper they published.

                “FastGlioma is an artificial intelligence-based diagnostic system that has the potential to change the field of neurosurgery by immediately improving comprehensive management of patients with diffuse gliomas,” said senior author Todd Hollon, a neurosurgeon at University of Michigan Health.

                “The technology works faster and more accurately than the current standard of care methods for tumor detection and could be generalized to other pediatric and adult brain tumor diagnoses. It could serve as a foundational model for guiding brain tumor surgery.”

                When a neurosurgeon removes a life-threatening tumor from a patient’s brain, they are rarely able to remove the entire mass. What remains is known as a residual tumor.

                Commonly, the tumor is missed during the operation because surgeons are not able to differentiate between healthy brain and residual tumor tissues in the cavity where the mass was removed.

                Neurosurgical teams employ different methods to locate that residual tumor during a procedure, which may include MRI imaging, which may not be available in the hospital, or a fluorescent imaging agent to identify tumor tissue, which is not applicable for all tumor types.

                These limitations prevent their widespread use.

                In this international study of the AI-driven technology, neurosurgical teams analyzed fresh, unprocessed specimens sampled from 220 patients who had operations for low or high-grade diffuse glioma.
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                • Sounds promising.

                  Scientists Discover Simple Supplement That Causes Prostate Cancer Cells To Self-Destruct

                  Vitamin K is found in leafy greens and is crucial for blood coagulation and calcium synthesis in tissues—but may also cure prostate cancer.

                  Not vitamin K specifically, but a precursor called menadione, which was found in a recent trial to interfere with the survival process of tumor cells and ultimately saw them explode.

                  Prostate cancer is one of the most lethal in men, and while multiple treatments exist, there are some varieties that are both highly resistant and highly aggressive. In 2001, a trial of 35,000 patients was funded to try and find out if vitamin E, a potent antioxidant, could help treat prostate cancer.

                  After just three years, however, it was found that more men taking the supplement started to get the disease. The trial organizers reasoned simply that if an antioxidant accelerated prostate cancer, could a pro-oxidant prevent it?

                  Researchers at Cold Spring Harbor Laboratory (CSHL) tested menadione, a precursor to vitamin K, in mice. In their animal model, it was found that the menadione depleted a lipid called PI(3)P, which works like an ID tag. Without it, the tumor cells failed to continue to recycle incoming material. They eventually exploded.

                  “It’s like a transport hub, like JFK. If everything that goes in is immediately de-identified, nobody knows where the airplanes should go next. New stuff keeps coming in, and the hub starts to swell. This ultimately leads to the cell bursting,” said Professor Lloyd Trotman, leader of the research from CSHL.
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                  • New Solution for Metastatic Ovarian Cancer Based on Approach From Nearly a Century Ago Shrinks Tumors

                    A novel combination resulted in tumor regression during preclinical lab testing by scientists at the nonprofit Wistar Institute in Philadelphia.

                    Ovarian cancer is the deadliest gynecological cancer, with low survival rates because it is naturally resistant to chemotherapy, so its presence is difficult to combat anywhere in the body.

                    The cancer tends to metastasize through peritoneal fluid in the peritoneal cavity—around the stomach and intestines—which is naturally immunosuppressive, so limits the body’s response to any tumors.

                    To combat the challenging cancer, Nan Zhang, Ph.D. and his collaborators turned to a possible solution from nearly a century ago.

                    In the late 1800s & early 1900s, New York surgeon William B. Coley achieved a cure rate greater than 10% for some cancers by injecting patients with dead pathogens. Scientists later reasoned that this anti-cancer effect was the result of the immune system’s activation of myeloid cells—the plentiful cells in the peritoneal cavity—that when activated can mount a cancer-killing response.

                    Building on the concept, Zhang’s team designed an approach that specifically activates myeloid cells within the peritoneal cavity through combination treatment with beta-glucan, a pathogen-derived activator of myeloid cells, and interferon-gamma (IFNγ).

                    Preliminary reports suggest the approach can work to reverse the immunosuppression around tumors, leading to positive results.
                    What is old is new again.
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                    • First Human Skin Map Provides 'Recipe' That Could Prevent Scarring And Facilitate Hair Transplants

                      Skin is the largest organ of the human body, measuring on average two square meters. It provides a protective barrier, regulates our body temperature and can regenerate itself.

                      But I bet you didn’t know that skin develops in the sterile environment of the womb, with all hair follicles formed before birth. (There is follicle cycling after birth, but no new follicles are made.)

                      Most importantly for the scientists behind a new report, before birth is when the skin has the unique ability to heal without scarring.

                      Now, for the first time, researchers have created a single cell atlas of prenatal human skin to understand how skin forms, and what goes wrong in disease—insights that could be used to create new hair follicles in regenerative medicine and transplants for burn victims.

                      Researchers from the Wellcome Sanger Institute at Newcastle University and their collaborators used single cell sequencing and other genomics techniques to create the atlas and uncover how human skin, including hair follicles, is formed.

                      For the study, published in Nature, the team also created a ‘mini organ’ of skin in a dish with the actual ability to grow hair.

                      Using the ‘organoid’, they showed how immune cells play an important role in scarless skin repair, which could lead to clinical applications to prevent scarring after surgery, or scarless healing after wounding.

                      “With our prenatal human skin atlas, we’ve provided the first molecular ‘recipe’ for making human skin and uncovered how human hair follicles are formed before birth,” said Dr. Elena Winheim, co-first author from the Wellcome Sanger Institute.
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                      • Cure for Pre-Eclampsia is On Horizon as Researcher Discovers Lipid Nanoparticle to Deliver Directly to Placenta

                        Engineers at the University of Pennsylvania have made a critical breakthrough that promises better outcomes for pregnancies threatened with pre-eclampsia, a condition that arises due to insufficient blood flow to the placenta, resulting in high maternal blood pressure and restricted blood flow to the fetus.

                        Pre-eclampsia is one of the leading causes of stillbirths and prematurity worldwide, and it occurs in 3 to 5% of pregnancies. Without a cure, options for these patients only treat symptoms, such as taking blood pressure medication, being on bed rest, or delivering prematurely—regardless of the viability of their baby.

                        Making a decision to treat pre-eclampsia in any manner can be a moral conundrum, to balance many personal health decisions with long-standing impacts—and for Kelsey Swingle, a doctoral student in the UPenn bioengineering lab, these options are not enough.

                        In previous research, she conducted a successful proof-of-concept study that examined a library of lipid nanoparticles (LNPs)—which are the delivery molecules that helped get the mRNA of the COVID vaccine into cells—and their ability to reach the placenta in pregnant mice.

                        In her latest study, published in Nature, Swingle examined 98 different LNPs and their ability to get to the placenta and decrease high blood pressure and increase vasodilation in pre-eclamptic pregnant mice.

                        Her work shows that the best LNP for the job was one that resulted in more than 100-fold greater mRNA delivery to the placenta in pregnant mice than an FDA-approved LNP formulation.

                        The drug worked.

                        “Our LNP was able to deliver an mRNA therapeutic that reduced maternal blood pressure through the end of gestation and improved fetal health and blood circulation in the placenta,” says Swingle.

                        “Additionally, at birth we saw an increase in litter weight of the pups, which indicates a healthy mom and healthy babies. I am very excited about this work and its current stage because it could offer a real treatment for pre-eclampsia in human patients in the very near future.”
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                        • Stanford Scientists Transform Ubiquitous Skin Bacterium into a Topical Vaccine Against Tetanus

                          Imagine a world in which a vaccine is a cream you rub onto your skin instead of a needle a health sector worker pushes into one of your muscles.

                          Even better, it’s cheap, entirely pain-free, and not followed by fever, swelling, redness, or a sore arm. No standing in a long line to get it either.

                          This is the vision that researchers at Stanford hope to achieve with a new tetanus vaccine derived from a bacterial species that’s found on the skins of virtually all human beings; one that’s largely harmless to us, yet nevertheless will trigger a ferocious antibody response if it breaches the skin barrier or gets inside the bloodstream.

                          A team of scientists led by the Standford Ph.D. in bioengineering Dr. Michael Fischbach hypothesized that Staphylococcus epidermidis, the harmless and ubiquitous bacterium, could be used as a delivery mechanism for the pathogen in a vaccine.

                          During experiments, Fischbach found that when the S. epidermidis bacteria were engineered to contain a small genetic trace of the tetanus bacteria, the immune system targeted it just as ferociously as before, while also resulting in a separate immune response to the tetanus gene of the kind one would expect from a vaccine.

                          The team learned through further examination of S. epidermidis that it naturally produces a large protein called Aap. This tree-shaped molecule is five times larger than normal proteins, and so large its ‘branches’ protrude from the cell wall. Fischbach and his team believe that this is the reason why the immune system’s response to this microbe is so robust: immune cells on our skin and hair follicles can study it even without coming in direct contact with it.

                          Mice, which have no native colonization of S. epidermidis, were found to have greater-than-vaccine level immune responses to this bug after it was swabbed directly onto their fur.

                          Fischbach and his team determined that this could be the basis for a topical vaccine, one in which the bacteria is engineered to carry the genetic material of humanity’s most dangerous diseases. Further tests carried out on the mice found that application of S. epidermidis engineered to carry tetanus generated enough antibodies to protect mice from six times the lethal dose of tetanus toxin—a truly astonishing discovery.
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                          • These are the things that could have a great impact on a great number of people.

                            These Tiny Implantable Sensors Helped Broken Bones Heal in Weeks Rather Than Months

                            Scientists have invented a set of tiny sensors that can help tailor rehabilitation programs for those recovering from broken bones.

                            Proper rehabilitation is key to ensuring the natural repair process is carried out correctly, and the devices offered crucial feedback that sped up this process in lab rats, allowing them to recover from femur fractures months ahead of schedule.

                            Developed by researchers at the University of Oregon, the sensors transmit real-time data about what’s happening at an injury site after being implanted in the body.

                            The team says that the sensors would allow physicians to monitor a patient’s progress and adjust exercises along the way to ensure they’re benefiting from the right amount of exercise.

                            They used the technology in a study, published in the journal NPJ Regenerative Medicine, to show that a resistance-training rehab program can “significantly improve” femur injuries in rats in just eight weeks. Most femoral fractures take around four to six months to heal completely.

                            “Our data support early resistance rehabilitation as a promising treatment to increase bone formation, bone healing strength, and promote full restoration of mechanical properties to pre-injury levels,” said senior author of the study, Professor Bob Guldberg.

                            It’s long been understood that post-injury exercise follows a Goldilocks principle: too little or too much can impede recovery, while just the right amount can enhance healing. However, pinpointing the exact type and intensity of exercise needed for the best recovery can be challenging, especially as it varies from patient to patient, and from bone to bone.

                            For their study, the researchers aimed to test whether resistance running, a specific type of recovery exercise, could provide the right mechanical stimulation to improve bone recovery.

                            To do that, they built custom brakes for rodent exercise wheels, which added resistance similar to increasing the level on an elliptical machine or stationary bike.

                            Rats with femur injuries and implanted sensors then ran on either a regular exercise wheel or the modified resistance exercise wheel.

                            The sensors transmitted strain data throughout the exercises, offering the research team a glimpse into the mechanical environment of bone cells during recovery.

                            Over the eight-week study, researchers monitored the healing process of the injured femurs and found that the resistance-trained rats displayed early signs of bone healing compared to those in sedentary or non-resistance conditions.
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