Tag: Medicine

Are Today’s Gynecologists Ignoring Women’s Health Issues?

Women’s health and wellbeing receive little attention compared to childbirth and reproduction, both in research and in clinic.

A new preliminary study from Tel Aviv University reveals that due to masculine dominance of the gynecological science field, most gynecological research focuses on childbirth and reproduction rather than women’s health and wellbeing. Mapping scientific journals in the category of gynecology and obstetrics, the study found that the majority deal with fertility, pregnancy, fetuses, and childbirth, while many topics that are much more critical to women’s quality of life receive little attention, both in scientific research and in the clinic.

The study was conducted by Dr. Netta Avnoon of the Department of Sociology and Anthropology and the Coller School of Management at Tel Aviv University. The preliminary results were published in the prestigious journal Nature Reviews Urology

 

“Men have dominated gynecology for almost a thousand years, and their gender identity impacts everything that happens in this specialty, including research design and medical practices.” Dr Netta Avnoon

 

Male Dominated Discipline

According to the preliminary study important issues that have been marginalized for centuries include diseases and damage to the muscles and nerves of the female pelvis and sexual organs, female sexual pleasure, rights and autonomy in childbirth, the connection between the menstrual cycle and the immune system, menopause, and the later years of life, and more.

“Men have dominated gynecology for almost a thousand years, and their gender identity impacts everything that happens in this specialty, including research design and medical practices,” says Dr. Avnoon. “Even if they are unaware of their own bias and have the best intentions, men traditionally regard the female body as an object for producing babies or satisfying men’s sexual desires. The time has come for women to dominate the discipline that is meant to care for their health.”

Dr. Avnoon explains that no social activity is neutral, objective or contextless, and science and medicine are no exception. Inevitably, social positions and dispositions impact the attitudes of those who create science.

Extensive historical and feminist scholarship has shown that gynecology as a medical specialty was masculinized 800 years ago, and still adheres to patriarchal values. In ancient times women were usually treated by women-experts, who even wrote books on the subject, but during the Middle Ages, these women and their knowledge were gradually ousted and replaced by men.

Since the 16th century the specialty has been wholly dominated by males, and consequently they were the ones to determine which topics are ‘interesting’ and worth studying; they were the ones who set practices and protocols and introduced treatments, technologies, and techniques, all too often subjecting patients to medical practices that are not necessarily benevolent.

 

Dr. Netta Avnoon

Exposing Current Focus

To expose the actual focus of gynecological research today, in line with previous feminist studies, Dr. Avnoon chose a tell-tale indicator: the titles of international scientific journals in the ‘gynecology and obstetrics’ category.

She analyzed the list appearing in the Journal Citation Reports, a database that provides general and statistical information about scientific journals worldwide, and the results were clear-cut: of the 83 journals listed by title in the category, 49% are dedicated solely to reproductive functions, pregnancy, fetuses, and childbirth; 24% focus on both gynecology and obstetrics; only 12% deal with health issues in the female sexual organs that are unrelated to reproductive functions; 6% deal with breasts; 5% deal with gynecological cancers; and a mere 4% (3 journals) address the health of women before and after childbearing age, including menopause.

Dr. Avnoon notes a recent instance of gynecology’s gender bias: the transvaginal mesh scandal. In 2019 the FDA banned the use of the transvaginal mesh – a common gynecological procedure used since the 1950s to repair pelvis organ prolapse in the anterior vaginal compartment, which had caused extensive morbidity and even 77 documented deaths in the USA.

Patients’ activism moved the regulator to intervene, exposing the decades-long failure of gynecological science to clinically assess the outcomes of this surgical procedure, and revealing the bias in how researchers presented these results in scientific publications.

 

“Care for the fetus, essential in its own right, must not come at the expense of the mother’s health.” Dr. Netta Avnoon

 

It’s Time: Women-Centered Gynecology

What solution does Dr. Avnoon have in mind? She proposes the following: “Obstetrics, focusing on fertility, reproduction, pregnancy, the fetus and childbirth, should be separated from gynecology, a specialty dedicated to women’s health.”

“Care for the fetus, essential in its own right, must not come at the expense of the mother’s health.”

“Also, gynecology training must include a major chapter of gender and feminist studies, and existing medical protocols should be amended to focus on the needs of the women – rather than those of their babies, their spouses, or their doctors. Moreover, legislation and legal procedures are in order, especially in courts of human rights, to protect women’s right to health and optimal medical care.”

“The time has come for women-centered gynecology,” says Dr. Avnoon. “Women’s voices must be heard.”

“To date, medical schools offer their students very scant and unsatisfactory knowledge about female anatomy and physiology, specifically in terms of women’s sexuality. Even though the overall numbers of female gynecologists are on the rise (in the US there are by now more women than men in this profession), their education is still based on age-old masculine and chauvinistic traditions.”

“In order to generate real change, doctors must be trained to regard women’s rights, health, and sexuality as the focus of women’s medicine, and to treat their patients with respect. Greater emphasis should be given to patient experience and autonomy in medical settings, and to much-needed innovation in research, instruments, technologies, protocols, surgical procedures, and medications.”

Removal of Cancerous Tumors Without Surgery

New technology from Tel Aviv University, combining ultrasound and nanobubbles, destroys tumors, eliminating need for invasive treatments.

A new technology developed at Tel Aviv University makes it possible to destroy cancerous tumors in a targeted manner, via a combination of ultrasound and the injection of nanobubbles into the bloodstream. Unlike invasive treatment methods or the injection of microbubbles into the tumor itself, this latest technology enables the destruction of the tumor in a non-invasive manner.

The study was conducted under the leadership of doctoral student Mike Bismuth from the lab of Dr. Tali Ilovitsh at Tel Aviv University’s Department of Biomedical Engineering, in collaboration with Dr. Dov Hershkovitz of the Department of Pathology. Prof. Agata Exner from Case Western Reserve University in Cleveland also participated in the study. The study was published in the journal Nanoscale.

 

 

“Our new technology makes it possible, in a relatively simple way, to inject nanobubbles into the bloodstream, which then congregate around ​​the cancerous tumor. After that, using a low-frequency ultrasound, we explode the nanobubbles, and thereby the tumor.”  Dr. Tali Ilovitsh

 

 

Bursting Bubbles – and Tumors

Dr. Tali Ilovitsh: “Our new technology makes it possible, in a relatively simple way, to inject nanobubbles into the bloodstream, which then congregate around ​​the cancerous tumor. After that, using a low-frequency ultrasound, we explode the nanobubbles, and thereby the tumor.”

The researchers explain that today, the prevalent method of cancer treatment is surgical removal of the tumor, in combination with complementary treatments such as chemotherapy and immunotherapy.

 

The research team

Therapeutic ultrasound to destroy the cancerous tumor is a non-invasive alternative to surgery. This method has both advantages and disadvantages. On the one hand, it allows for localized and focused treatment; the use of high-intensity ultrasound can produce thermal or mechanical effects by delivering powerful acoustic energy to a focal point with high spatial-temporal precision. This method has been used to effectively treat solid tumors deep within in the body. Moreover, it makes it possible to treat patients who are unfit for tumor resection surgery. The disadvantage, however, is that the heat and high intensity of the ultrasound waves may damage the tissues near the tumor.

 

 

“The combination of nanobubbles and low frequency ultrasound waves provides a more specific targeting of the area of the tumor and reduces off-target toxicity.” Dr. Tali Ilovitsh

 

 

Reducing Off-target Damage

In the current study, Dr. Ilovitsh and her team sought to overcome this problem. In the experiment, which used an animal model, the researchers were able to destroy the tumor by injecting nanobubbles into the bloodstream (as opposed to what has been until now, which is the local injection of microbubbles into the tumor itself), in combination with low-frequency ultrasound waves, with minimal off-target effects.

“The combination of nanobubbles and low frequency ultrasound waves provides a more specific targeting of the area of the tumor, and reduces off-target toxicity,” explains Dr. Ilovitsh.

“Applying the low frequency to the nanobubbles causes their extreme swelling and explosion, even at low pressures. This makes it possible to perform the mechanical destruction of the tumors at low-pressure thresholds.”

“Our method has the advantages of ultrasound, in that it is safe, cost-effective, and clinically available, and in addition, the use of nanobubbles facilitates the targeting of tumors because they can be observed with the help of ultrasound imaging.”

Dr. Ilovitsh adds that the use of low-frequency ultrasound also increases the depth of penetration, minimizes distortion and attenuation, and enlarges the focal point. “This can help in the treatment of tumors that are located deep with the body, and in addition facilitate the treatment of larger tumor volumes. The experiment was conducted in a breast cancer tumor lab model, but it is likely that the treatment will also be effective with other types of tumors, and in the future, also in humans.”

New Hope for Patients with Severe Bone Loss

Researchers induced bone regeneration with a special hydrogel that mimics the bone’s natural environment.

An innovative technology developed at Tel Aviv University will enable bone regeneration to correct large bone defects by means of a special hydrogel. Following successful tests in a lab model, the researchers now plan to move forward to clinical trials.

The groundbreaking study was conducted by experts from TAU’s Maurice and Gabriela Goldschleger School of Dental Medicine, led by Prof. Lihi Adler-Abramovich and Dr. Michal Halperin-Sternfeld, in collaboration with Prof. Itzhak Binderman, Dr. Rachel Sarig, Dr. Moran Aviv, and researchers from the University of Michigan in Ann Arbor. The paper was published in the Journal of Clinical Periodontology.

Prof. Adler-Abramovich: “Small bone defects, such as fractures, heal spontaneously, with the body restoring the lost bone tissue. The problem begins with large bone defects. In many cases, when substantial bone loss results from tumor resection (removal by surgery), physical trauma, tooth extraction, gum disease or inflammation around dental implants, the bone is unable to renew itself. In the current study, we developed a hydrogel that mimics the natural substances in the extracellular matrix of bones, stimulating bone growth and reactivating the immune system to accelerate the healing process.”

The researchers explain that the extracellular matrix is the substance surrounding our cells, providing them with structural support. Every type of tissue in our body has a specific extracellular matrix consisting of suitable substances with the right mechanical properties. The new hydrogel has a fibrillary structure that mimics that of the extracellular matrix of the natural bone. Furthermore, it is rigid, thus enabling the patient’s cells to differentiate into bone-forming cells.

 

WATCH: Lab of Bioinspired Materials: A Tour with TAU Prof. Lihi Adler-Abramovich

 

“As can be expected, the extracellular matrix of our bones is quite rigid,” says Prof. Adler-Abramovich. “In our study, we produced a hydrogel that mimics this specific matrix in both chemical and physical properties. At the nanometric level, the cell can attach itself to the gel, gaining structural support and receiving relevant mechanical signals from the fibers. At first, to test these properties, we grew cells in a 3D model of the gel. Then we examined the impact of the hydrogel on model animals with large bone defects that could not heal spontaneously. We monitored them for two months with various methods, including Micro C.T. To our delight, the bone defects were fully corrected through regeneration, with the bones regaining their original thickness, and generating new blood vessels.”

According to Prof. Adler-Abramovich, the innovative gel has extensive clinical applications in both orthopedic and dental medicine: “When we lose teeth due to extensive damage or bacterial infections, the standard treatment is dental implants. Implants, however, must be anchored in a sufficient amount of bone, and when bone loss is too substantial, physicians implant additional bone from a healthy part of the body – a complex medical procedure. Another option is adding bone substitutes from either human or animal sources, but these might generate an immune response. I hope that in the future the hydrogel we have developed will enable faster, safer, and simpler bone restoration.”  

Featured image: The research team

Pressure Chamber Therapy Effective in Improvement of Autism

TAU study shows that treatment may significantly improve social abilities and condition of the autistic brain.

A new Tel Aviv University study succeeded in significantly improving social skills and the condition of the autistic brain through pressure chamber therapy. The study was conducted on lab models of autism. In it, the researchers identified changes in the brain, including a reduction in neuroinflammation, which is known to be associated with autism. Moreover, a significant improvement was found in the social functioning of the animal models treated in the pressure chamber. The study’s success has many implications regarding the applicability and understanding of treating autism using pressure chamber therapy.

The breakthrough was made under the leadership of doctoral student Inbar Fischer, from the laboratory of Dr. Boaz Barak of Tel Aviv University’s Sagol School of Neuroscience and School of Psychological Sciences. The research was published in the International Journal of Molecular Sciences.

Considered Safe

Fischer and Barak explain that hyperbaric medicine is a form of therapy in which patients are treated in special chambers where the atmospheric pressure is higher than the pressure we experience at sea level, and in addition are delivered 100 percent oxygen to breathe.

Hyperbaric medicine is considered safe and is already being used to treat a long list of medical conditions, including here in Israel. In recent years, scientific evidence has been accumulating that unique protocols of hyperbaric treatments improve the supply of blood and oxygen to the brain, thereby improving brain function.

Improving Brain Function

“The medical causes of autism are numerous and varied, and ultimately create the diverse autistic spectrum with which we are familiar,” explains Dr. Barak:. “About 20% of autistic cases today are explained by genetic causes, that is, those involving genetic defects, but not necessarily ones that are inherited from the parents. Despite the variety of sources of autism, the entire spectrum of behavioral problems associated with it are still included under the single broad heading of ‘autism,’ and the treatments and medications offered do not necessarily correspond directly to the reason why the autism developed.”

In the preliminary phase of the study, a girl carrying the mutation in the SHANK3 gene, which is known to lead to autism, received treatments in the pressure chamber, conducted by Prof. Shai Efrati, director of the Sagol Center for Hyperbaric Medicine at the Shamir “Assaf Harofeh” Medical Center, faculty member at the Sagol School of Neuroscience, and a partner in the study. After the treatments, it was evident that the girl’s social abilities and brain function had improved considerably.

In the next stage, and in order to comprehend the success of the treatment more deeply, the team of researchers at Dr. Barak’s laboratory sought to understand what being in a pressurized chamber does to the brain. To this end, the researchers used lab models carrying the same genetic mutation in the SHANK3 gene as that carried by the girl who had been treated. The experiment comprised a protocol of 40 one-hour treatments in a pressure chamber over several weeks.

“We discovered that treatment in the oxygen-enriched pressure chamber reduces inflammation in the brain and leads to an increase in the expression of substances responsible for improving blood and oxygen supply to the brain, and therefore brain function,” explains Dr. Barak. “In addition, we saw a decrease in the number of microglial cells, immune system cells that indicate inflammation, which is associated with autism.”

 Increased Social Interest

“Beyond the neurological findings we discovered, what interested us more than anything was to see whether these improvements in the brain also led to an improvement in social behavior, which is known to be impaired in autistic individuals,” adds Dr. Barak. “To our surprise, the findings showed a significant improvement in the social behavior of the animal models of autism that underwent treatment in the pressure chamber compared to those in the control group, who were exposed to air at normal pressure, and without oxygen enrichment. The animal models that underwent treatment displayed increased social interest, preferring to spend more time in the company of new animals to which they were exposed in comparison to the animal models from the control group.”

Inbar Fischer concludes, “the mutation in the animal models is identical to the mutation that exists in humans. Therefore, our research is likely to have clinical implications for improving the pathological condition of autism resulting from this genetic mutation, and likely also of autism stemming from other causes. Because the pressure chamber treatment is non-intrusive and has been found to be safe, our findings are encouraging and demonstrate that this treatment may improve these behavioral and neurological aspects in humans as well, in addition to offering a scientific explanation of how they occur in the brain.”

Featured image: Members of the TAU research team (left to right): Dr. Nour Ershaid, Prof. Neta Erez and Lea Monteran (Photo Credit: TAU)

Breakthrough Treatment May Improve Efficacy of Chemotherapy in Breast Cancer Patients

TAU-developed treatment may reduce risk for lung metastasis following chemo from 52% to only 6%.

A new treatment developed at Tel Aviv University may significantly enhance the efficacy of chemotherapy in breast cancer patients, reducing the risk for lung metastasis following chemo from 52% to only 6%. Conducted in a lab model, the study identified the mechanism that generates a cancer-promoting inflammatory environment in response to chemotherapy. Moreover, the researchers found that by adding an anti-inflammatory agent to the chemotherapy, metastasis can be prevented.

The study was led by Prof. Neta Erez of the Department of Pathology at TAU’s Sackler Faculty of Medicine, and researchers from her group: Lea Monteran, Dr. Nour Ershaid, Yael Zait, and Ye’ela Scharff, in collaboration with Prof. Iris Barshack of the Sheba Medical Center and Dr. Amir Sonnenblick of the Tel Aviv Sourasky (Ichilov) Medical Center. The paper was published in Nature Communications. The study was funded by ERC, the Israel Cancer Association, and the Emerson Cancer Research Fund.

The Dark Side of Chemo

“In many cases of breast cancer, surgical removal of the primary tumor is followed by a chemotherapy regimen intended to kill any remaining malignant cells – either left behind by the surgeon or already colonizing in other organs,” explains Prof. Erez. “However, while effectively killing cancer cells, chemotherapy also has some undesirable and even harmful side effects, including damage to healthy tissues. The most dangerous of these, is probably internal inflammations that might paradoxically help remaining cancer cells to form metastases in distant organs. The goal of our study was to discover how this happens and try to find an effective solution.”

To this end, the researchers created an animal model for breast cancer metastasis. The animals received the same treatment as human patients: surgical removal of the primary tumor, then chemotherapy, followed by monitoring to detect metastatic relapse as early as possible. The disturbing results: metastatic tumors were detected in the lungs of a large percentage of the treated animals – similar to the percentage found in the control group.

 

“In humans, this interval between chemotherapy and detection of metastatic tumors is an inaccessible ‘black box.’ Working with an animal model, we could check what happens inside this ‘box’.” Prof. Neta Erez

 

What’s Going on Inside the “Black Box”?

To decipher these adverse effects, the researchers examined the animals’ lungs at an intermediate stage – when tiny micro-metastases may have already developed, but even advanced imaging technologies like CT cannot detect them.

“In humans, this interval between chemotherapy and detection of metastatic tumors is an inaccessible ‘black box’,” says Prof. Erez. “Working with an animal model we could check what happens inside this ‘box’.”

“We discovered a previously unknown mechanism: the chemotherapy generates an inflammatory response in connective tissue cells called ‘fibroblasts’, causing them to summon immune cells from the bone marrow. This, in turn, creates an inflammatory environment that supports the micro-metastases, helping them grow into full-fledged metastatic tumors. In this way, the chemotherapy, administered as a means for combating cancer, achieves the opposite result.”

The researchers also identified the mechanism through which fibroblasts recruit immune cells, and ‘train’ them to support the cancer. “We found that in response to chemotherapy, the fibroblasts secrete ‘complement proteins’ – proteins that mediate cell recruitment and intensify inflammation, often by summoning white blood cells to damaged or infected areas, a process called chemotaxis,” notes Prof. Erez. “When the immune cells reach the lungs, they create an inflammatory environment that supports cancer cells and helps them grow.”

 

“We identified an inflammatory mechanism through which chemotherapy inadvertently supports the growth of metastatic tumors, and also discovered an effective solution: combining chemotherapy with an inflammation inhibitor.” Prof. Neta Erez

 

Potential to Save Many Lives

To combat this newly discovered process, the researchers combined the chemotherapy administered to the animals with a drug that blocks the activity of complement proteins.

The results were very encouraging: following the combined treatment, the percentage of lab models developing no metastases rose from 32% to 67%; and the percentage of those with extensive cancer colonization in their lungs decreased from 52% with regular chemotherapy to 6% when the inflammation inhibitor was added.

“We discovered the mechanism behind a severe problem in the treatment of breast cancer: many patients develop metastatic tumors following removal of the primary tumor plus chemotherapy,” says Prof. Erez, and concludes: “We identified an inflammatory mechanism through which chemotherapy inadvertently supports the growth of metastatic tumors, and also discovered an effective solution: combining chemotherapy with an inflammation inhibitor. We hope that our findings will enable more effective treatment for breast cancer, and perhaps other types of cancer as well – to prevent metastatic relapse and save numerous lives worldwide.”  

Featured image: Members of the TAU research team (left to right): Dr. Nour Ershaid, Prof. Neta Erez and Lea Monteran

Ukrainian Citizens Display High Resilience Amid Fighting

Ukrainian People show more national resilience than Israelis did during Operation “Guardian of the Walls”.

A first-of-its-kind study conducted by Tel Aviv University has found that the national resilience of the citizens of Ukraine, who are currently fighting for their independence, is comparatively very high (4.35) on a scale of 1 to 6. It is, in fact, significantly higher than the national resilience that characterized Israeli citizens (3.89) at the height of “Operation Guardian of the Walls” in May 2021.

The researchers explain this difference by saying that whereas Ukrainian citizens now find themselves fighting for their homeland and are ready to do anything to win the war, the rounds of fighting in Gaza have become a kind of recurrent nuisance for the citizens of Israel, accompanied by a moderate level of national resilience.

The study was led by Prof. Bruria Adini and Prof. Shaul Kimhi of the ResWell Research Center at Tel Aviv University’s Sackler Faculty of Medicine.

Ukrainian Citizens Still Have Hope

According to the researchers, the current study constitutes the first attempt by academic researchers to assess Ukrainian citizens’ positive and negative coping indices during wartime. The study indicates that in such conditions of conflict, a population may experience high levels of stress and, simultaneously, high levels of societal resilience and hope for the future.

In the current situation in Ukraine, the population has also demonstrated a great deal of support for their government.

The study surveyed 1000 Ukrainian citizens, as well as a sample of about 650 Israeli citizens using data collected during Operation Guardian of the Walls. The study’s findings suggest that the danger, in the eyes of Ukrainian citizens, is perceived as much more tangible (3.7 on a scale of 1 to 5) than Israelis’ perception of danger in the rounds of fighting against Hamas in Gaza (2.45). The perception of threat amongst Ukrainians is also more significant (3.29) than among the citizens of Israel (2.79).

The researchers note that the younger population, those between the ages of 26 to 30, present higher levels of stress and post-traumatic stress symptoms compared to other age groups. Women report higher levels of all negative coping mechanisms in comparison to men.

Interestingly, despite the significant dangers and threats they face, Ukrainian citizens have not lost hope, with their ‘hope index’ being higher (an average of 3.95) than that of Israelis (an average of 3.5).

 

“Israelis, unlike the Ukrainian People, do not feel that their country is under a direct existential threat and have, to a certain degree, adapted to an ‘emergency routine’ due to the recurrent conflicts.” Prof. Adini and Prof. Kimhi

 

Israelis Adapted to ‘Emergency Routine’

Prof. Adini and Prof. Kimhi explain that “the perception of a threat as existential to the survival and sovereignty of the state and society is likely, under certain conditions, to enhance the population’s societal resilience and sense of hope. This is the case even when the population feels anxious and threatened by the situation. “

“Moreover, it appears that the war launched by Russia against Ukraine has actually contributed to the process of Ukrainian identity-building, which also leads to increased levels of resilience, as well as an extremely high sense of hope.”

“Israelis, unlike the Ukrainian People, do not feel that their country is under a direct existential threat and have, to a certain degree, adapted to an ‘emergency routine’ due to the recurrent conflicts. In light of this, they present lower levels of resilience relative to Ukrainians, but at the same time higher levels of well-being and morale.”

Improving the Well-being of Women with BRCA Gene, Responsible for Breast Cancer

Unique technique found by Tel Aviv University researchers to improve emotional well-being of women with increased risk of breast cancer, assist in decision making.

Many young women with increased risk of breast cancer (carriers of BRCA1/BRCA2 genes) suffer from a state of uncertainty regarding their future, mainly due to the realization that they are highly likely to contract breast cancer and/or ovarian cancer. There is currently no effective treatment for preventing the illness and the only active procedure available is a risk-reducing mastectomy [surgery to remove a breast] and/or oophorectomy [a surgical procedure to remove one or both ovaries] around the age of 40 (it was this procedure that Angelina Jolie underwent in 2013).

Due to fear and uncertainty, these women often suffer psychological and physical symptoms that significantly disrupt their normal lives. In a new study conducted at Tel Aviv University, researchers sought to examine whether workshops and tools for promoting personal health, relief of stress and tension, and strengthening of mental soundness can improve the emotional well-being and quality of sleep of these young women. The researchers determined that use of the Inquiry Based Stress Reduction (IBSR) technique can be very helpful in coping with stressful events, enhance emotional and psychological well-being, improve quality of sleep, and assist in decision making.

Doing “The Work”

The study was led by Dr. Shahar Lev-Ari of the Sackler Faculty of Medicine at Tel Aviv University, in cooperation with Prof. Eitan Friedman of Sheba Medical Center and assistance from other researchers, as part of PhD student Clara Landau’s dissertation. The study was published in the prestigious medical journal JAMA Network Open.

The study included 100 women, all carriers of BRCA1/BRCA2 genes and currently under supervision at the Meirav Breast Center at Sheba Medical Center. As part of the study, the women learned and practiced the IBSR method, a clinical application of “The Work” by Byron Katie, consisting of a mindful self-inquiry for increased mindfulness, work on stress-causing beliefs (the “Inquiry” process) for reduction of stress, and cognitive reframing.

Dr. Shahar Lev-Ari

 

“To the best of our knowledge, this is the largest ever study in the world in the framework of such an experiment, as far as the number of participants is concerned.” 

 

Significant Improvements

The results were impressive. After participating in the workshops, as well as self-practice, the women showed great improvement in all aspects of personal growth, positive relations with others, life goals, and self acceptance. A clear improvement was seen in quality of sleep, which returned to normal.

Furthermore, a clear change of attitude was found among the participants with regard to previous doubts over whether to undergo surgical procedures such as mastectomy and oophorectomy. The technique helped the women make rational medical decisions, and some changed their position from ruling out the option of having any procedure done to scheduling a doctor’s appointment to discuss the option.

The researchers believe their findings indicate that study and practice of IBSR techniques might improve the psychological well-being of women with BRCA1/BRCA2 gene mutations, and form the basis (in conjunction with other studies) for recommending to consider providing this technique to women, along with their oncogenetic consultation.

“To the best of our knowledge, this is the largest ever study in the world in the framework of such an experiment, as far as the number of participants is concerned,” says Dr. Shahar Lev-Ari.

“We think that healthcare services in Israel and worldwide should evaluate the impact of coping with the genetic information and surgical procedures offered to asymptomatic women carriers on their emotional well-being and quality of life, and offer them interventions to promote their health on the individual level, such that have been scientifically proven in improving the quality of life and emotional well-being of women with the BRCA1/BRCA2 genes,” he summarizes.

Slowing Down Skin Cancer

Tel Aviv University researchers decipher the mechanism that enables skin cancer to metastasize to the brain – delaying its spread by 80%.

Once melanoma, or skin cancer, spreads to the brain, it becomes extremely aggressive. Individuals with this stage of cancer are given an average 15 months to live, and that is following surgery, radiation, and chemotherapy. Researchers from Tel Aviv University deciphered, for the first time, a mechanism that enables skin cancer to metastasize to the brain and managed to delay the spread of the disease by 60% to 80% (depending on the stage of the intervention) using existing treatments.

 

The encouraging study was led by Prof. Ronit Satchi-Fainaro and Ph.D. student Sabina Pozzi of the Sackler Faculty of Medicine at Tel Aviv University. The results were published in the scientific journal JCI Insight.

 

“In an advanced stage, 90% of melanoma patients will develop brain metastases. This is a puzzling statistic. We expect to see metastases in the lungs and liver, but the brain is supposed to be a protected organ.”

 

How do the Cancer Cells Infiltrate the Brain?

“In an advanced stage, 90% of melanoma [/skin cancer] patients will develop brain metastases,” explains Prof. Satchi-Fainaro. “This is a puzzling statistic. We expect to see metastases in the lungs and liver, but the brain is supposed to be a protected organ. The blood-brain barrier keeps harmful substances from entering the brain, and here it supposedly doesn’t do the job—cancer cells from the skin circulate in the blood and manage to reach the brain. We asked ourselves with ‘whom’ the cancer cells ‘talk’ to in the brain to infiltrate it.”

 

The researchers found that in melanoma patients with brain metastases, the cancer cells “recruit” cells called ‘astrocytes’, star-shaped cells found in the spinal cord and brain which are responsible for maintaining stable conditions (/homeostasis) in the brain.

 

“The astrocytes are the first to come to correct the situation in the event of a stroke or trauma, for example,” says Prof. Satchi-Fainaro, “and it is with them that the cancer cells interact, exchanging molecules and corrupting them.”

 

Protecting the Brain’s Border Guards

“Moreover, the cancer cells recruit the astrocytes so that they do not inhibit the spread of the metastases. As such, they create local inflammation in the melanoma cells-astrocytes interaction areas that increase the permeability through the blood-brain barrier, as well as the division and migration of the cancer cells.”

 

“The communication between them is reflected in the fact that the astrocytes begin to secrete a protein that promotes inflammation called MCP-1 (also known as CCL2), and in response to this, the cancer cells begin to express its receptors CCR2 and CCR4, which we suspected to be responsible for the destructive communication with the astrocytes.”

 

“Both the antibody and the small molecule we used (…) have already been tested on humans as part of clinical trials. Therefore, these treatments are considered safe, and we can try to repurpose them for melanoma.”

 

To test their hypothesis, Prof. Satchi-Fainaro and her team tried to inhibit the expression of the protein and its receptors in genetically engineered lab models and in 3D models of primary melanoma and brain metastases. To this end, the researchers used both an antibody (biological molecule) and a small molecule (synthetic), designed to block the MCP-1 protein. They also employed CRISPR technology, a gene-editing technique, to genetically edit the cancer cells and cut out the two genes that express the two relevant receptors, CCR2 and CCR4. With each of the methods, the researchers were able to delay the spread of metastases.

 

“These treatments succeeded in delaying the penetration of the cancer cells into the brain and their subsequent spread throughout the brain,” says Prof. Satchi-Fainaro. The team succeeded in achieving a 60% to 80% delay, depending on the stage of the intervention. They achieved the best results with the treatment conducted immediately after surgery to remove the primary melanoma and were able to prevent the metastases from penetrating the brain.

 

“I believe that the treatment is suitable for the clinic as a preventive measure,” says Satchi-Fainaro. “Both the antibody and the small molecule we used—which are primarily intended to treat sclerosis, diabetes, liver fibrosis, and cardiovascular diseases, as well as serve as a biomarker for other types of cancer—have already been tested on humans as part of clinical trials. Therefore, these treatments are considered safe, and we can try to repurpose them for melanoma.”

 

The research was conducted in collaboration with additional scientists and physicians from Tel Aviv University, including Prof. Adi Barzel, Dr. Asaf Madi, Prof. Iris Barshack, Prof. Eran Perlson, and Prof. Inna Slutsky. International researchers also participated in the study, including Prof. Eytan Ruppin from the US National Institutes of Health (NIH), Prof. Henry Brem and Thomas Hyde from Johns Hopkins University-, and Prof. Helena Florindo from the University of Lisbon.

 

The study was funded by the European Research Council (ERC), the Melanoma Research Alliance (MRA), the Kahn Foundation, the Israel Cancer Research Fund (ICRF), and the Israel Science Foundation (ISF).

 

Featured image: Ph.D. student Sabina Pozzi and Prof. Ronit Satchi-Fainaro

Covid-19 Antibodies May Eliminate Need for Boosters

Breakthrough TAU discovery can neutralize all known Covid variants.

A team of Tel Aviv University researchers has demonstrated that antibodies isolated from the immune system of recovered COVID-19 patients are effective in neutralizing all known strains of the virus, including the Delta and the Omicron variants. The discovery may eliminate the need for repeated booster vaccinations and strengthen the immune system of populations at risk.

 

The research was led by Dr. Natalia Freund and doctoral students Michael Mor and Ruofan Lee of the Department of Clinical Microbiology and Immunology at the Sackler Faculty of Medicine and of the TAU Center for Combating Pandemics. The study was conducted in collaboration with Dr. Ben Croker of the University of California San Diego. Prof. Ye Xiang of Tsinghua University in Beijing. Prof. Meital Gal-Tanamy and Dr. Moshe Dessau of Bar-Ilan University also took part in the study. The study was published in the Nature journal Communications Biology.

 

Highly Effective Against Delta and Omicron

The present study is a continuation of a preliminary study conducted in October 2020, at the height of the COVID-19 crisis. At that time, Dr. Freund and her colleagues sequenced all the B immune system cells from the blood of people who had recovered from the original COVID strain in Israel, and isolated nine antibodies that the patients produced. The researchers now found that some of these antibodies are very effective in neutralizing the new coronavirus variants, Delta and Omicron.

 

“In the previous study, we showed that the various antibodies that are formed in response to infection with the original virus are directed against different sites of the virus,” says Dr. Freund. “The most effective antibodies were those that bound to the virus’s ‘spike’ protein, in the same place where the spike binds the cellular receptor ACE2. Of course, we were not the only ones to isolate these antibodies, and the global health system made extensive use of them until the arrival of the different variants of the coronavirus, which in fact rendered most of those antibodies useless.”

 

“In the current study, we proved that two other antibodies, TAU-1109 and TAU-2310, which bind the viral spike protein in a different area from the region where most of the antibodies were concentrated until now (and were therefore less effective in neutralizing the original strain) are actually very effective in neutralizing the Delta and Omicron variants. According to our findings, the effectiveness of the first antibody, TAU-1109, in neutralizing the Omicron strain is 92%, and in neutralizing the Delta strain, 90%. The second antibody, TAU-2310, neutralizes the Omicron variant with an efficacy of 84%, and the Delta variant with an efficacy of 97%.”

 

Can Serve as Effective Substitute for Boosters

According to Dr. Freund, the surprising effectiveness of these antibodies might be related to the evolution of the virus: “The infectivity of the virus increased with each variant because each time, it changed the amino acid sequence of the part of the spike protein that binds to the ACE2 receptor, thereby increasing its infectivity and at the same time evading the natural antibodies that were created following vaccinations.”

 

“In contrast, the antibodies TAU-1109 and TAU-2310 don’t bind to the ACE2 receptor binding site, but to another region of the spike protein – an area of ​​the viral spike that for some reason does not undergo many mutations – and they are therefore effective in neutralizing more viral variants. These findings emerged as we tested all the known COVID strains to date.”

 

“In our view, targeted treatment with antibodies and their delivery to the body in high concentrations can serve as an effective substitute for repeated boosters, especially for at-risk populations and those with weakened immune systems.” 

 

The two antibodies, cloned in Dr. Freund’s laboratory at Tel Aviv University, were sent for tests to check their effectiveness against live viruses in laboratory cultures at the University of California San Diego, and against pseudo viruses in the laboratories of the Faculty of Medicine of Bar-Ilan University in the Galilee; the results were identical and equally encouraging in both tests.

 

Dr. Freund believes that the antibodies can bring about a real revolution in the fight against COVID-19: “We need to look at the COVID-19 pandemic in the context of previous disease outbreaks that humankind has witnessed. People who were vaccinated against smallpox at birth and who today are 50 years old still have antibodies, so they are probably protected, at least partially, from the monkeypox virus that we have recently been hearing about. Unfortunately, this is not the case with the coronavirus. For reasons we still don’t yet fully understand, the level of antibodies against COVID-19 declines significantly after three months, which is why we see people getting infected again and again, even after being vaccinated three times.”

 

“In our view, targeted treatment with antibodies and their delivery to the body in high concentrations can serve as an effective substitute for repeated boosters, especially for at-risk populations and those with weakened immune systems. COVID-19 infection can cause serious illness, and we know that providing antibodies in the first days following infection can stop the spread of the virus. It is therefore possible that by using effective antibody treatment, we will not have to provide booster doses to the entire population every time there is a new variant.”

Featured image: Dr. Natalia Freund from the Sackler Faculty of Medicine (Photo: Yoram Reshef)

Scientific discovery may facilitate speedy, objective, and accurate diagnosis of the condition using saliva

Scientific discovery may facilitate speedy, objective, and accurate diagnosis of the condition using saliva.

A scientific breakthrough from the Tel Aviv and Haifa Universities may facilitate speedy, objective, and accurate diagnosis of people suffering from posttraumatic stress disorder, PTSD, using saliva samples, as well as developing microbiotic related medications (associated with the body’s microbial ecology).

 

The study was a joint effort by eminent scholars from various fields. It was led by Professor Illana Gozes and included Professor Noam Shomron, Dr. Shlomo Sragovich and Ph.D. student Guy Shapira, (all from TAU’s Sackler Faculty of Medicine and Sagol School of Neuroscience) as well as Prof. Zahava Solomon from TAU’s Gershon H. Gordon Faculty of Social Sciences, and Prof. Abraham Sagi-Schwartz and PhD student Ella Levert-Levitt from the Center for the Study of Child Development and the School of Psychological Sciences at Haifa University. The study was published in NATURE‘s prestigious MOLECULAR PSYCHIATRY magazine.

 

Diagnosing PTSD by Objective Criteria

The researchers tested a unique group of about 200 Israeli veteran soldiers (they all came from a larger cohort of subjects from a comprehensive four-decade-long study of veterans by Prof. Solomon) who had fought in the first Lebanon War in 1982. The test covered various psychological aspects, including sleep, appetite disorders, guilt, suicidal thoughts, social and spousal support, hostility, satisfaction with life, as well as issues of demographics, psychopathology, welfare, health, and education.

 

“We were surprised to discover that about a third of the PTSD subjects had never been diagnosed with post-trauma, so they never received any recognition from the Ministry of Defense and the official authorities.”

 

The researcher also collected saliva samples from them and comparing the results of the subjects’ microbial distribution to the psychological results and their responses to the welfare questionnaires, the researchers from the universities of Tel Aviv and Haifa found that people with PTSD and high psychopathological indications exhibit the same picture of bacteria in the saliva (a unique oral microbiotic signature).

According to the researchers, this study is significant in that for the first time, we might be able to diagnose post-trauma by objective criteria and not just behavioral ones.

One Third of Soldiers Were Undiagnosed

It is interesting to note here that the saliva bacteria of those exposed to air pollution showed a correlation to the picture with PTSD, while the number of years of education showed a protective influence and a reverse picture of the microbial ecology in the saliva. 

 

“To the best of our knowledge, this is the first depiction of a microbial signature in the saliva among veteran soldiers with PTSD,” says Prof. Illana Gozes. “We were surprised to discover that about a third of the PTSD subjects had never been diagnosed with post-trauma, so they never received any recognition from the Ministry of Defense and the official authorities.”

 

“To the best of our knowledge, this is the first depiction of a microbial signature in the saliva among veteran soldiers with PTSD,”

 

“It must be stressed that until now, post-trauma diagnosis has been based solely on psychological and psychiatric measures. Thanks to this study, it may be possible, in the future, to use objective molecular and biological characteristics to distinguish PSTD sufferers, taking into account environmental influences. We hope that this new discovery and the microbial signatures described in this study might promote easier diagnosis of post-traumatic veteran soldiers so they can receive appropriate treatment.”

The study was also supported by IDF’s Medical Corps Department of Health and Well-Being and Dr. Ariel Ben Yehuda, former chief of the above Department and currently, a Department Manager in the Mental Health Medical Center in Shalvata, Clallit Health Services. The study also involved collaboration with the Charité University Medicine in Berlin and its microbiology experts Dr. Markus M. Heimesaat and Professor Stefan Bereswill, as well as with the University of Hong Kong, which is studying the effects of air pollution, Professors Victor Li and Jacqueline Lam.

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