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One Third of Normal-Weight Individuals are Obese

Research

Jul 12th, 2023
One Third of Normal-Weight Individuals are Obese

Researchers at Tel Aviv University found that the widely used Body Mass Index (BMI) measurement is less sensitive to define obesity than we thought

  • Medicine

Researchers from the School of Public Health at Tel Aviv University's Faculty of Medicine examined the anthropometric [the scientific study of the measurements and proportions of the human body] data of about 3,000 Israeli women and men and concluded that body fat percentage is a much more reliable indicator of an individual's overall health and cardiometabolic risk than the BMI index, widely used in clinics today. The researchers suggest that body fat percentage should become the gold standard in this respect and recommend equipping clinics all over Israel with suitable devices.

 

 

"BMI (…) is considered a standard indicator of an individual's general health. However, despite the obvious intuitive connection between excess weight and obesity, the actual measure for obesity is the body's fat content." – Prof. Yftach Gepner

 

 

'The Paradox of Obesity with Normal Weight'

The study - the largest of its kind ever conducted in Israel - was led by Prof. Yftach Gepner and PhD student Yair Lahav, in collaboration with Aviv Kfir. It was based on data from the Yair Lahav Nutrition Center in Tel Aviv.  The paper was published in Frontiers in Nutrition.

 

"Israel is a leader in childhood obesity and more than 60% of the country's adults are defined as overweight," says Prof. Gepner, adding that, "the prevailing index in this respect is BMI, based on weight and height measures, which is considered a standard indicator of an individual's general health. However, despite the obvious intuitive connection between excess weight and obesity, the actual measure for obesity is the body's fat content, with the maximum normal values set at 25% for males and 35% for females. Higher fat content is defined as obesity and can cause a range of potentially life-threatening cardiometabolic diseases: heart disease, diabetes, fatty liver, kidney dysfunction, and more. The disparity between the two indexes has generated a phenomenon called 'the paradox of obesity with normal weight' – higher than normal body fat percentage in normal-weight individuals. In this study we examined the prevalence of this phenomenon in Israel's adult population."

 

 

"We recommend equipping all clinics with suitable devices for measuring body fat content, and gradually turning it into the gold standard both in Israel and worldwide, to prevent disease and early mortality." - Prof. Yftach Gepner

 

 

Body Fat Percentage – A More Reliable Indicator

The researchers analyzed the anthropometric data of 3,000 Israeli women and men, accumulated over several years: BMI scores; DXA scans (using X-rays to measure body composition, including fat content); and cardiometabolic blood markers.  About one third of the participants, 1,000 individuals, were found to be within the normal weight range.  Of these, 38.5% of the women and 26.5% of the men were identified as 'obese with normal weight' – having excess fat content despite their normal weight. Matching body fat percentage with blood markers for each of these individuals, the study found a significant correlation between 'obesity with normal weight' and high levels of sugar, fat, and cholesterol – major risk factors for a range of cardiometabolic diseases.  At the same time, 30% of the men and 10% of the women identified as overweight were found to have a normal body fat percentage.

 

"Our findings were somewhat alarming, indicating that obesity with normal weight is much more common in Israel than we had assumed," warns Prof. Gepner. "Moreover, these individuals, being within the norm according to the prevailing BMI index, usually pass 'under the radar'. Unlike people who are identified as overweight, they receive no treatment or instructions for changing their nutrition or lifestyle - which places them at an even greater risk for cardiometabolic diseases."

 

Based on their findings, the researchers concluded that body fat percentage is a more reliable indicator of an individual's general health than BMI. Consequently, they suggest that body fat percentage should become the prevailing standard of health and recommend some convenient and accessible tools for this purpose: skinfold measurements that estimate body fat based on the thickness of the fat layer under the skin; and a user-friendly device measuring the body's electrical conductivity, already used in many fitness centers.

   

Prof. Gepner: "Our study found that obesity with normal weight is very common in Israel, much more than we had previously assumed, and that it is significantly correlated with substantial health risks. And yet, people who are 'obese with normal weight' are not identified by today's prevailing index, BMI. We also found that body fat percentage is a much more reliable indicator than BMI with regard to an individual's general health. Therefore, we recommend equipping all clinics with suitable devices for measuring body fat content, and gradually turning it into the gold standard both in Israel and worldwide, to prevent disease and early mortality."

Operation Guardian of the Walls: Women, Young People and Residents of the South Paid the Heaviest Price

Research

Jul 12th, 2023
Operation Guardian of the Walls: Women, Young People and Residents of the South

Smartwatches prove that residents of the south suffered significantly more harm than the rest of the population

  • Life Sciences
  • Medicine

During Operation Guardian of the Walls, which took place in May 2021, researchers from Tel Aviv University carried out a groundbreaking study by equipping Israelis with smartwatches and a dedicated mobile application. The study aimed to examine the impact of the operation on the well-being of citizens by monitoring various objective and subjective indicators. The findings revealed that residents of Israel's southern region suffered significantly more than the rest of the population.

 

Assessing Impacts, as well as Resilience

The innovative study was conducted by a team of researchers from Tel Aviv University: Prof. Erez Shmueli, Prof. Dan Yamin, and Ph.D. students Merav Mofaz and Matan Yechezkel of The Iby and Aladar Fleischman Faculty of Engineering; Prof. Noga Kronfeld-Schor of The George S. Wise Faculty of Life Sciences; and Prof. Haim Einat of the Academic College of Tel Aviv-Yafo. The findings of the groundbreaking study were published in the journal Communication Medicine from the Nature group.

 

According to Prof. Erez Shmueli, the study was part of a broader initiative called PerMed (Personalized Medicine), aimed at early diagnosis of infectious diseases like COVID-19. However, the timing of Operation Guardian of the Walls presented a unique opportunity to examine the physiological and mental changes experienced by civilians during wartime.

 

By May 2021, the researchers had enrolled 954 Israelis in the experiment, equipping them with smartwatches to assess the impact of the war on the home front. The data collected from the smartwatches and participants' reports through the app revealed a significant deterioration in various metrics during the war compared to normal circumstances. Notably, after the war ended, all indicators returned to their previous levels on average, showcasing the mental resilience of Israelis. Nevertheless, the researchers observed notable differences among Israeli citizens: with residents of the southern areas (near Gaza), exposed to frequent and dangerous rocket attacks, enduring more significant mental and physiological effects compared to those in the central regions. Furthermore, central region residents suffered more than those in the north.

 

 

"In future research, it is crucial to identify individuals who experienced significant adversity during the war and did not fully recover following its conclusion. We believe that providing prompt and targeted support to these individuals may prevent the development of post-traumatic stress disorder (PTSD)." - Prof. Erez Shmueli

 

 

The findings highlighted several key differences among the citizens. For example, residents of the southern areas spent more time (6.2 hours) looking at their screens compared to central region residents (5.3 hours), and central region residents spent more screen time than those in the north (5 hours). Similar patterns emerged in other metrics, such as mood (3.24 in the south versus 3.45 in the center and 3.75 in the north, on a scale of 1 to 5), stress (2.8 in the south versus 2.6 in the center and 2.3 in the north, on a scale of 1 to 5), physical activity (20 minutes in the south compared to about 34 minutes in the center and in the north), sleep duration (6.1 hours in the south compared to 6.2 hours in the center and 6.5 hours in the north) and quality of sleep (2.9 in the south compared to 3.3 in the center and 3.5 in the north, on a scale of 1 to 5). Women and young people experienced more deviation from their normal patterns during the conflict compared to men and adults.

 

Since Operation Guardian of the Walls, there have been subsequent rounds of fighting between Israel and factions in Gaza, as well as Russia's invasion of Ukraine. Prof. Shmueli believes that wearable technology holds immense potential in monitoring the consequences of such conflicts and providing aid to populations in need: “In the past, wars were fought at the borders,” says Prof. Shmueli. “Today, they are fought deep within the country. Therefore, monitoring the resilience of citizens is crucial, both as groups and as individuals. The state needs to know what happens to its citizens during war, as well as provide special support to groups that are more prone to harm. In future research, it is crucial to identify individuals who experienced significant adversity during the war and did not fully recover following its conclusion. We believe that providing prompt and targeted support to these individuals may prevent the development of post-traumatic stress disorder (PTSD).”

Prof. Shai Meiri

Research

Jul 12th, 2023
Due to Climate Change, More Animals will Become Extinct Outside of Nature

According to int'l study surveying more than 14,000 species of amphibians and reptiles

  • Life Sciences
  • Biology
  • Environment

A new international study has found that amphibians and reptiles inhabiting the world’s nature reserves, or Protected Areas (PAs), will be better protected against climate change than species found outside of these areas, but are still likely to be harmed.

 

The research findings provide evidence, on a global scale, of the crucial role Protected Areas play in conserving amphibian and reptile biodiversity under human-induced climate change scenarios. The study reveals that more animals will become extinct because of climate change outside of Protected Areas than inside them — in the world in general and on most individual continents.

 

Protected Areas as Refuges

Prof. Shai Meiri of Tel Aviv University’s School of Zoology, The George S. Wise Faculty of Life Sciences and The Steinhardt Museum of Natural History took part in the study, in collaboration with leading researchers from 19 countries. The study was published in the prestigious journal Nature Communications.

 

 

"Approximately 91% of the amphibian and reptile species we examined are protected, to some degree, in Protected Areas, and this proportion will remain unchanged under future climate change." - Prof. Shai Meiri

 

 

The purpose of the study was to evaluate the effectiveness of existing Protected Areas in protecting the amphibians and reptiles living within them under future climate scenarios, as well as to identify conservation gaps in order to outline a road map for the development of conservation actions based on the current global network of Protected Areas.

 

“In this study, we collected distribution data for more than 14,000 species of amphibians and reptiles — about 70% of the known species — to perform a global assessment of the conservation effectiveness of Protected Areas in an era of climate change, using species distribution models," explains Prof. Meiri. "Our analyses revealed that approximately 91% of the amphibian and reptile species we examined are protected, to some degree, in Protected Areas, and that this proportion will remain unchanged under future climate change. Furthermore, species protected in Protected Areas will lose smaller portions of their distribution ranges inside the nature reserve than outside of them. Therefore, the proportion of species within reserves is expected to increase.”

 

Relative Optimism

However, Prof. Meiri points out, “We predict that more than 300 of the amphibian species and 500 of the reptile species we studied will become extinct due to climate change in the coming decades, and probably also hundreds of species for which we did not have sufficient data to model. Our research highlights the importance of Protected Areas in providing refuge for amphibians and reptiles in face of climate change and points out areas where there are not enough nature reserves that can better preserve biodiversity around the world.”

 

 

"Despite the relative optimism emerging from the new research, the models still predict extremely high rates of loss of species and habitats due to climate change. Protected Areas do indeed protect the animals living within them, but nothing is foolproof." - Prof. Shai Meiri

 

 

He adds: “We compiled a comprehensive global database with more than 3.5 million observation records spanning 5,403 amphibian species and 8,993 reptile species from online databases, fieldwork data, museum collections, and published references. For all species in our database, we predicted habitat availability according to current (1960–1990) climate data and future scenarios (for the years 2060–2080) at a high spatial resolution (1 km × 1 km) using species distribution models. Then, we evaluated the effectiveness of Protected Areas in conserving amphibians and reptiles by calculating the coverage of their distribution range inside and outside of Protected Areas, as well as the proportion of species for whom a significant portion of their distribution range (for example, 15% or 30%) is protected in PAs under current and future climate conditions (assuming that the future use of the land remains unchanged over the years — that is, that there will be no conversion of nature reserves into agricultural, industrial, or urban areas.)”

 

Prof. Meiri concludes: “Our evidence shows that the current global network of Protected Areas already plays an important role in preserving the global biodiversity of amphibians and reptiles, and will continue to do so under the expected future climate. However, many species do not live in the existing Protected Areas. These include, for example, many amphibians and reptiles in Mexico, Jamaica, the Andes, West Africa, South Africa, the southern and northern coast of Turkey, Yemen and other places. Moreover, in our study we could create a model for only about two-thirds of reptile and amphibian species. Good models can’t be created for the rarest species, which are known to be more vulnerable to extinction and less protected in Protected Areas. At the same time, it is important to remember that despite the relative optimism emerging from the new research, the models still predict extremely high rates of loss of species and habitats due to climate change. Protected Areas do indeed protect the animals living within them, but nothing is foolproof.”

Discovery May Lead to Personalized Medicine for Infectious Diseases

Research

Jul 11th, 2023
Discovery May Lead to Personalized Medicine for Infectious Diseases

Tel Aviv University researchers open new doors for applying personalized medicine to infectious diseases, moving beyond cancer and Alzheimer's

  • Life Sciences
  • Medicine

In the world of healthcare, personalized medicine has made significant strides in certain disease areas, notably cancer. However, when it comes to infection diseases, the application of personalized medicine tools remains largely unexplored. Thanks to a groundbreaking scientific breakthrough, researchers at Tel Aviv University have set their sights on expanding the realm of personalized medicine to encompass infectious diseases as well. This newfound potential holds the promise of delivering more targeted and effective treatments to patients in need.  

 

Until now, the medical world studied the immune response as a single unit, but a team of researchers at Tel Aviv University discovered a way, using experiments and computational tools, to classify two central components of the immune response that operate as a result of severe infectious disease. The importance of the discovery is that it provides a doorway to the world of personalized medicine in the field of infectious diseases and the provision of more effective treatments for patients. For example, instead of deciding to give a uniform medicine to all patients (i.e. an antibiotic like penicillin) the physician will be able to determine precisely which medicine he should give the patient and at what dosage, according to the classification of the infection based on analysis of the ratio between two key markers found in the patient’s blood.

 

Zooming in on the Immune System

The research was led by Prof. Irit Gat-Viks and Prof. Eran Bacharach, with the doctoral students Ofir Cohn and Gal Yankovitz from the Shmunis School of Biomedicine and Cancer Research in The George S. Wise Faculty of Life Sciences. The study was published in the prestigious journal, Cell Systems.

 

 

"From simple blood tests, we can learn a lot about the health status of people who became ill and give them more comprehensive treatment according to the development of the infection in their bodies." - Prof. Irit Gat-Viks

 

 

"In the general population, people react differently to infections, and therefore there is a need for medical tools to indicate how each person is expected to react to a certain infectious disease," explains Prof. Gat-Viks. She explains that, "until now, there have been only very general indicators to characterize these diseases, such as inflammatory markers, fever, urine tests, etc. Based on these indicators, analyses of the response to the infection that appeared rather uniform can be divided into different responses according to the new classification. In extreme cases, as we saw in the Corona epidemic, a person's immune response to the virus can result in lethality, and preliminary identification of their response can help us save lives. Our new observations and more precise classification of the inflammatory response has allowed us to identify new indicators and markers in our bloodstream. What all this means is that from simple blood tests, we can learn a lot about the health status of people who became ill and give them more comprehensive treatment according to the development of the infection in their bodies."

 

Prof. Eran Bacharach and Prof. Irit Gat-Viks

 

The researchers were able to observe the response of the immune system with high resolution, and identify two main types of responses. Prof. Bacharach outlines the first response as one in which, "the immune system fights a pathogen that has entered the body," and the other type and one in which "the damage to the body 'after the war' with the pathogen is repaired." In their research, they used disease models in animals, computational tools, and information collected from people with different markers in their bodies that are indicators of the type of response to the pathogen.

 

 

"People with extreme reactions to infection with microorganisms such as viruses or bacteria lack an adequate medical response today." - Prof. Irit Gat-Viks

 

 

Prof. Gat-Viks explains that "in fact, personalized medicine exists today for 'regular' diseases such as cancer, but there is almost no use of personalized medicine methods in the field of infectious diseases. People with extreme reactions to infection with microorganisms such as viruses or bacteria lack an adequate medical response today. We believe that thanks to our research, doctors will be able to better diagnose the patient's condition and, as a result, provide effective treatment that will improve the patient's chances of recovery. We aim to continue the research and discover more subgroups with different reactions among the population so that we can help doctors make their diagnosis more precise and thus provide proper treatment for their patients."

Healthy child happily playing soccer/football with his father

Research

Jun 27th, 2023
Breakthrough Gene Therapy Offers Hope for Severe Developmental Epilepsy in

Advancing treatment and improving quality of life

  • Medicine

Researchers at Tel Aviv University, among other institutions, have developed an innovative gene therapy that may help children suffering from Dravet syndrome (DS), a severe developmental epilepsy caused by a random mutation in the SCN1A gene during fetal development. DS is characterized by uncontrollable epilepsy, developmental delays, cognitive impairment, and a high risk of early death. The team's innovative gene therapy not only improved epilepsy but also protected against early death and enhanced cognitive abilities in DS lab models.

 

Breakthrough Gene Therapy

The researchers are hopeful that their genetic therapy can be adapted for other genetic epilepsies and may lead to the development of similar treatments for rare diseases. The study involved injecting a virus carrying a normal SCN1A gene into the brains of DS mice. The treatment demonstrated effectiveness in various critical aspects, even after the onset of severe epilepsy. The researchers express optimism that their laboratory technique will eventually reach clinical settings and provide help to children wit this debilitating disease. They also believe that the tools developed during this research will pave the way for similar treatments for other rare diseases.  

 

The study was led by Dr. Moran Rubinstein and graduate student Saja Fadila, along with Anat Mavashov, Marina Brusel and Karen Anderson, all from the Sackler Faculty of Medicine and the Sagol School of Neuroscience at Tel Aviv University, and Dr. Eric Kremer, from the University of Montpellier in France. Also participating in the study were Bertrand Beucher and Iria González-Dopeso Reyes from Montpellier and other researchers from France, the USA and Spain. The research was published in the Journal of Clinical Investigation.

 

Dr. Moran Rubinstein

 

Dravet syndrome affects approximately one in 16,000 births and is considered relatively common among rare genetic diseases. Currently, there are around 70 affected children in Israel. The syndrome presents as thermally-induced seizures around six months of age, with progress to frequent spontaneous epileptic seizures and motor and cognitive developmental delays after one year.

 

Dr. Rubinstein highlights that existing epilepsy drugs are insufficient for children with DS, who face a significant risk of early death. The syndrome results from a genetic mutation that occurs randomly during fetal development in a gene called SCN1A and is not inherited from the parents. Unfortunately, the disease cannot be predicted or discovered during pregnancy, making early diagnosis challenging.

 

According to the researchers, it is customary nowadays to perform a genetic analysis for children who suffer from complex thermally-induced seizures around the age of six months. However, even if the test detects that the problem is in the SCN1A gene, the final diagnosis is often given after the epilepsy worsens, with the appearance of severe spontaneous convulsions and developmental delays. Although it is important to have an early diagnosis, diagnosis is often delayed, and most children are diagnosed only at the age of one or two years and sometimes even later.

 

Promising Results in Lab Models

Although genetic therapies have shown promise in DS mice and some of them are undergoing clinical trials in humans, they have only been effective when administered at very early stages, prior to symptom onset. Given the complex and invasive nature of gene therapy, it cannot be administered without a confirmed diagnosis of DS. Hence, the researchers focused on developing a treatment that could be effective after seizure onset, even at a relatively late age. Additionally, since DS involves cognitive impairments, the team aimed to alleviate both epilepsy and cognitive symptoms.

 

Dr. Rubinstein explains that viruses are commony used as carriers in genetic therapies to introduce normal genetic material into patients, enabling normal cellular function. For this purpose, the virus is engineered: its original genetic material is removed so it cannot cause disease or replicate itself, and instead, the relevant normal gene is packed inside. In the case of Dravet syndrome, since the SCN1A gene is very large, it was not possible to use common viruses that are usually used for this purpose and a virus capable of carrying and transferring large genes was needed. The team solved this problem by using a virus called Canine adeno virus type 2, as a carrier of the normal gene.

 

The carrier virus was directly injected into the brains of DS mice since its properties prevent it from crossing the blood-brain barrier. The treatment was administered to 31 mice at three weeks of age,  after spontaneous convulsions had commenced (equivalent to one to two years of age in children), and to 13 mice at five weeks of age (equivalent to approximately six to eight years of age in children). The injection was performed in multiple brain areas, while an empty virus was injected into the brains of 48 control mice.

 

Potential for Rare Diseases

Promising results followed, with the highest efficacy observed when the treatment was administered at three weeks of age. In these mice, seizures ceased entirely within 60 hours of injection, life expectancy significantly increased, and cognitive impairment, assessed through spatial memory tests, was completely restored. Even in mice treated at five weeks of age, there was notable improvement, characterized by reduced epileptic activity and protection against thermally-induced seizures. In the control group that received the empty virus, no improvement was observed, and the mice experienced symptoms akin to untreated mice, with approximately 50% succumbing to early death due to severe epilepsy. The treatment was also applied to healthy mice without any adverse effects, demonstrating its safety.

 

The researchers clarify that their treatment restored normal function to damaged neurons in the brain by introducing a complete, normal gene. This approach is crucial in treating Dravet syndrome since the mutation can occur at different locations within the gene, and administering a complete gene provides a univform treatment suitable for all DS patients. Furthermore, the chosen virus infected numerous nerve cells and spread widely beyond the injection site, enhancing its effectiveness.  

 

Dr. Rubinstein concludes that their treatment is the first proven to be effective for Dravet syndrome after the onset of spontaneous convulsions, offering improvement in cognitive function for DS mice. The team has already registered a patent, and hopes to see the treatment reach clinical settings to benefit children affected by this debilitating disease. They are also exploring its potential applicability to other genetic neurodevelopmental diseases. The developed platform represents a plug-and-play system for genetic therapies, with the possibility of incorporating different types of normal genetic material into the carrier virus for treating additional diseases in the future.

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