The Croatian National Tourist Board, together with its partner in international markets, the PR agency Grayling, won the prestigious “PR Report Award” in the “Consumer Marketing” category in strong competition from world-famous companies such as Microsoft and Colgate-Palmolive.The ceremonial and 14th awards ceremony was held last night in Berlin, organized by the independent German magazine PR Report, which is intended for PR professionals and public relations experts. “I am extremely glad that we won this prestigious award because it only confirms what we have been communicating intensively lately, and that is a new direction in promotional activities that the Croatian National Tourist Board started two years ago. Our PR and marketing activities are integrated, we know exactly who we are addressing, in what way and in which market. We also have global partners in foreign markets who, together with our representative offices, serve us as additional strategic support. The Croatian tourist brand is, figuratively speaking, getting stronger every day, and the won awards for us at the same time represent satisfaction and motivation for further actions.”, Said director Ivičić, adding that this tourist year, in addition to tourist traffic and revenue, is a record for the awards and recognitions won.As they point out from the CNTB when applying for the tender, they applied for and described so far successfully implemented and realized projects such as “Around the World in One Country”, “Croatia Loves You”, “We’ll see you in Croatia”. and all under the communication concept of “Full of Life”. See more about all the winners at PR Report Award
“We expect that the next tourist year will also be a record, and in the Ministry of Tourism the growth is expected to be at the level of five percent,” said the State Secretary in the Ministry of Tourism. Frano Matušić at the fourth session of the Tourist Business Council at the Croatian Chamber of Commerce, held on December 21 at the Croatian Chamber of Commerce. He added that they have entered the preparations ambitiously and that they will work on changes to the legal framework in order to improve the infrastructure in tourism.”Amendments to the Law on Tourist Boards, amendments to the Law on Tourist Tax will be implemented, and a proposal for amendments to the Law on Tourist Land will be prepared with the working group. The CroCard project aims to contribute to a stronger incentive for domestic guests, especially for continental tourism. With the program of competence centers and the cooperation of all relevant institutions, it is planned to conduct targeted education and retraining for tourism occupations. Congress tourism will be encouraged again, and the plan is to open three large congress centers in Croatia”, Said Matusic.”This year’s and last year’s tourist season were successful and well done, they contributed significantly to investments in the hotel sector and we believe that this trend will continue.”, Said the Vice President of the Croatian Chamber of Commerce for Tourism, Trade and Finance Josip Zaher He added that the Croatian Chamber of Commerce will continue to strongly combine domestic production with tourism, with a specialized campaign ‘Let’s buy a Croatian – Croatian product for Croatian tourism’, as a stimulus to economic growth.Josip Zaher, Frano Matušić, Franco Palma and Antonija Urlić; Source: HGK.”For the tourist year 2017, it is necessary to do the promotion and sales extremely professionally”, Said the president of TPV at the Croatian Chamber of Commerce Franco Palma and added that the biggest step forward in tourism was made by hoteliers with numerous investments. “This year, investments in tourism amounted to 676 million euros. Next year it will amount to 817 million euros, of which 500 million euros will be from the private sector, and 42 new hotels will be renovated and opened.”, Said Matušić.”In the first ten months of this year, Croatia made a total of 15 million tourist arrivals, which is 8,3% more than the previous year, and the same with 70,6 million overnight stays, which is 8,8% more than last year.”, Said the director of the Sector for Market Research and Strategic Planning of the CNTB Igor Borojevic. Next year in Croatia, better results are expected in the tourist pre-season and the overall growth in tourist overnight stays by 3,3%, said Borojević.The presidents of associations and communities at the Croatian Chamber of Commerce and the presidents of national associations pointed out a key issue that is a limitation for further development within a certain activity. Ultimately, everyone agrees that further growth requires changes in legislation that will follow the real needs of the tourism industry: the Law on the provision of services in tourism, the Law on Maritime Property and Seaports, the Law on Tourist Land, the Law on Concessions and legislation related to by the operation of the system of tourist boards. The tourism sector agrees on the need to revise the VAT rate and the taxation system of travel agencies, which objectively continue to be an obstacle to the growth of profitability of the entire sector.Director of the Tourism Department of the Croatian Chamber of Commerce Leila Krešić-Jurić She pointed out that the Tourist Business Council at the Croatian Chamber of Commerce is a unique body that brings together 19 national associations at the Croatian Chamber of Commerce and external associations and thus represents the entire tourism sector in Croatia. In addition to measures related to changes in legislation, she pointed out the proposal to introduce a flat income tax for all micro and small entities, with revenues of up to one million kuna per year, stimulating year-round operation of various activities in tourism.Source: HGK
Email LinkedIn Share Share on Facebook Although opioids are frequently prescribed to treat chronic lower back pain, new research suggests these powerful medications may be less effective in some patients. A study published in the Online First edition of Anesthesiology, the official medical journal of the American Society of Anesthesiologists® (ASA®), found patients who were prescribed opioids to treat chronic lower back pain experienced significantly less pain relief and were more likely to abuse their medication when they had psychiatric disorders such as depression or anxiety.“High levels of depression and anxiety are common in patients with chronic lower back pain,” said Ajay Wasan, M.D., study author and professor of anesthesiology and psychiatry at the University of Pittsburgh School of Medicine. “Learning that we are able to better predict treatment success or failure by identifying patients with these conditions is significant. This is particularly important for controlled substances such as opioids, where if not prescribed judiciously, patients are exposed to unnecessary risks and a real chance of harm, including addiction or serious side effects.”Chronic lower back pain affects 50 million adults in the United States. Patients with lower back pain may experience depression or anxiety in response to their chronic pain. Share on Twitter In the prospective cohort study, researchers examined 55 chronic lower back pain patients with low- to-high levels of depression or anxiety symptoms. Patients were given morphine, oxycodone or a placebo to take orally for the pain as needed over a six-month period. Patients recorded their pain levels and the doses taken daily.Patients with high levels of depression or anxiety experienced 50 percent less improvement in back pain (21 percent vs. 39 percent pain improvement), 75 percent more opioid abuse (39 percent vs. eight percent), and increased side effects when compared to patients with low levels of depression or anxiety symptoms.“It’s important for physicians to identify psychiatric disorders prior to deciding whether to prescribe opioids for chronic back pain as well as treat these conditions as part of a multimodal treatment plan,” said Dr. Wasan. “Rather than refusing to prescribe opioids, we suggest that these conditions be treated early and preferably before lower back pain becomes chronic. For those prescribed opioids, successful treatment of underlying psychiatric disorders may improve pain relief and reduce the chance of opioid abuse in these patients.”The authors note that further testing is needed to confirm whether treating psychiatric disorders early in the course of lower back pain can solely improve pain and function without the use of opioids or other treatments. Pinterest
Email LinkedIn Share on Twitter Pinterest Scientists at the Centre for Genomic Regulation (CRG), the research company Starlab and the group BR::AC (Barcelona Research Art & Creation) of the University of Barcelona developed a device that produces sounds from brain signals. This highly interdisciplinary team is led by Mara Dierssen, head of the Cellular & Systems Neurobiology group at CRG.Its ultimate goal is to develop an alternative communication system for people with cerebral palsy to allow them to communicate–and more specifically in this pilot phase, to communicate their emotions. Scientists are carrying out the project with volunteers who are either healthy or who have physical and/or mental disabilities, working together with the association Pro-Personas con Discapacidades Físicas y Psíquicas (ASDI) from Sant Cugat del Vallès.“At the neuroscientific level, our challenge with Brain Polyphony is to be able to correctly identify the EEG signals–that is, the brain activity–that correspond to certain emotions. The idea is to translate this activity into sound and then to use this system to allow people with disabilities to communicate with the people around them. This alternative communication system based on sonification could be useful not only for patient rehabilitation but also for additional applications, such as diagnosis,” stated Mara Dierssen. She added, “Of course, the technological and computational aspects are also challenging. We have to ensure that both the device and the software that translates the signals can give us robust and reproducible signals, so that we can provide this communication system to any patient.” Share on Facebook Share Currently, other signal transduction systems (using brain-computer interfaces) are undergoing testing for people with disabilities. However, most of these systems require a certain level of motor control, for example, by using eye movement. This represents a major constraint for people with cerebral palsy, who often suffer from spasticity or who are unable to control any aspect of their motor system, making it impossible for them to use these systems. A further limitation is that most of these other devices do not allow real-time analysis of the signals but rather require information post-processing. The proposal put forth by the Brain Polyphony researchers now allows real-time analysis, starting from the moment the user puts on the interface device.The sound of our brainUnlike other existing sonification systems using brain signals, Brain Polyphony allows us to directly “hear” brainwaves. “For the first time, we are using the actual sounds of brain waves. We assign octaves (as they are amplified) until we reach the range audible to the human ear, so that what we hear is really what is happening in our brain. The project aims to achieve this sound and to identify a recognizable pattern for each emotion that we can translate into code words. And all of this happens instantaneously in real-time,” explained David Ibáñez, researcher and project manager of Starlab.Until now, the device has been tested mainly with healthy people, but the most recent tests with people with disabilities have been pleasantly surprising. The device was also presented at the 2015 Sónar festival in Barcelona, where it enhanced the artistic expression of the event by allowing users to “hear” the music created by their emotions. Along this line, Efraín Foglia, researcher at BR::AC, University of Barcelona, added: “The mere fact that we are able to hear our brains “talk” is a complex and interesting experience. With Brain Polyphony, we are able to hear the music that is broadcast directly from the brain. This is a new form of communication that will take on a unique dimension if it can also allow us to enable people with cerebral palsy to communicate.”Bringing science to market, a challenge for research centresThis project not only exemplifies the importance of collaborations between scientific disciplines but also provides a success story in how to bring basic research to society. Brain Polyphony was the result of an internal initiative of the Center for Genomic Regulation (CRG), which seeks to promote multidisciplinary approaches and mainstreaming of basic research focused on patients and society, especially at an early stage. “We encourage our researchers at CRG to propose translational and collaborative projects that should involve clinics or other companies in the health sector groups. For that, we created an internal call to grant additional seed funding, to allow them to do risky and innovative projects and ideas. The idea is to encourage them to try an initial project that they can then use after a year to make the leap to applying for more ambitious and competitive funding. Brain Polyphony shows how important institutional support, like the CRG commitment, can be to such projects”, concluded Michela Bertero, responsible for the Scientific and International Affairs office at CRG.
Share Share on Facebook Researchers at Karolinska Institutet and the Sahlgrenska Academy in Sweden might be one step closer to finding an effective drug for alcohol dependence. In two separate studies, they show that the dopamine stabilizer OSU6162 can reduce the craving for alcohol in alcohol dependent people and normalises the level of dopamine in the brain reward system of rats that have consumed alcohol over a long period of time. However, thorough clinical studies are needed to determine if the OSU6162 also can help alcohol dependent people drink less alcohol. Share on Twitter LinkedIn Pinterest “The results of our studies are promising, but there is still a long way to go before we have a marketable drug,” says Pia Steensland, Associate Professor at the Department of Clinical Neuroscience, Karolinska Institutet and co-author of both studies. “The socioeconomic costs of alcohol are huge, not to mention the human suffering. It is inspiring to continue working.”Roughly a million Swedes over 15 years of age drink so much alcohol that they risk damaging their health, and it is estimated that some 300,000 of these people are dependent. Despite the pressing need, there are only a few approved drugs for the treatment of alcohol dependence, but their effects vary from person to person and the prescriptions rates are low. Consequently the hunt for new, more efficacious drugs for alcohol dependence continues. Email Clinical studyThe studies of OSU6162 are based on the knowledge of how the brain reward system stimulates us to act in the interests of our own survival. Since dopamine creates a feeling of wellbeing, such as when we exercise or eat good food, the memory associates the two so that we will repeat the behaviour. Alcohol makes the brain reward system release more dopamine than normal, creating a pleasant euphoric sensation. However, the more alcohol drunk, the more the reward system is desensitised and the less dopamine is released. With time, greater volumes of alcohol are needed to cause intoxication and eventually to attain a state of physical and emotional normality – addiction has set in.In the clinical study, which is published in the scientific journal European Neuropsychopharmacology¸ the scientists examined for the first time if OSU6162 can reduce the craving for alcohol in people with alcohol dependence. Half the participants were treated with OSU6162 and half with placebo for a fortnight, after which both groups were exposed to different situations that could be assumed to elicit a craving for alcohol. The results show that the experimental group experienced less of a craving for alcohol after drinking one glass of an alcoholic beverage.“At the same time, the OSU6162 group reported not enjoying the first zip of alcohol as much as the placebo group,” says Dr Steensland. “One interesting secondary finding was that those with the poorest impulse control, that is those thought to be most at risk of relapse after a period of abstinence, were those who responded best to the OSU6162 treatment.”Adds to the understandingA study of rats published at the same time in the scientific journal Addiction Biology adds to the understanding of how OSU6162 works, as it shows that rats that voluntarily consumed alcohol for almost a year had lower levels of dopamine in their brain reward system than rats that had never drunk alcohol. However, when the “alcohol rats” were treated with OSU6162 it was found that the substance counteracted the low concentrations of dopamine in the brain reward system.“We therefore think that OSU6162 can reduce the alcohol craving in dependent people by returning the downregulated levels of dopamine in their brain reward system to normal,” says Dr Steensland.The rights to OSU6162 are owned by Nobel Laureate Arvid Carlsson, professor emeritus at the Sahlgrenska Academy, University of Gothenburg, whose team also invented the substance. Emeritus Professor Carlsson is also one of the co-authors of the clinical study. The research was financed with grants from several bodies, including the Swedish Brain Foundation, the Swedish Research Council, the Torsten Söderberg Foundation, Systembolaget’s alcohol research council and the Swedish Research Council for Health, Working Life and Welfare (FORTE).
Wisdom is often linked with age, but not all elders are wise. So, what makes a person wise?A new study, “The Relationship between Mental and Somatic Practices and Wisdom,” published Feb. 18, 2016, in PLOS ONE, confirms the age-old conception that meditation is associated with wisdom. Surprisingly, it also concludes that somatic (physical) practices such as classical ballet might lead to increased wisdom.“As far as I know this is the first study to be published that looks at the relationship between meditation or ballet and increased wisdom,” said Monika Ardelt, associate professor of sociology at the University of Florida. Ardelt is a leading wisdom researcher who was not involved in the project. “That meditation is associated with wisdom is good to confirm, but the finding that the practice of ballet is associated with increased wisdom is fascinating. I’m not going to rush out and sign up for ballet, but I think this study will lead to more research on this question.” Share Pinterest Share on Facebook Email LinkedIn Share on Twitter The researchers included ballet in the study, “not expecting to find that it was associated with wisdom, but rather for comparison purposes,” said Patrick B. Williams, lead author and a postdoctoral researcher in the University of Chicago’s Department of Psychology. Williams is a member of a research project on somatic wisdom headed by principal investigators Berthold Hoeckner, associate professor of music; and Howard Nusbaum, professor of psychology.“The link between ballet and wisdom is mysterious to us and something that we’re already investigating further,” Williams said. This includes ongoing studies with adult practitioners of ballet, as well as among novices training at Chicago’s Joffrey Ballet. Williams wants to track novices and seasoned practitioners of both meditation and ballet for months and years to see whether the association holds up over time.The published research was groundbreaking because science has overlooked somatic practices as a possible path to wisdom, Williams said.Unstudied topic“No studies have examined whether physical practices are linked to the cultivation of personal wisdom, nor have they theorized that this association might exist,” the study stated.Understanding the kinds of experiences that are related to increases in wisdom is fundamental in two aspects of the UChicago research, Nusbaum said.“As we learn more about the kinds of experiences that are related to wisdom, we can gain insight into ways of studying the mechanisms that mediate wisdom. This also lets us shift from thinking about wisdom as something like a talent to thinking about it as something more like a skill,” he said. “And if we think about wisdom as a skill, it is something we can always get better at, if we know how to practice.”The researchers administered a self-reported survey to 298 participants using Survey Monkey, a popular Internet-based tool that is being used increasingly in scientific research. The survey asked about experience (both in number of years and hours of practice) as a teacher or student of four activities: meditation, the Alexander Technique (a method for improving posture, balance, coordination, and movement), the Feldenkrais Method (a form of somatic education that seeks to improve movement and physical function, reduce pain, and increase self-awareness), and classical ballet. It also included psychological questionnaires that asked about characteristics thought to be components of wisdom, such as empathy and anxiety.The results showed that those who practice meditation–vipassana (29 percent), mindfulness (23 percent), Buddhist (14 percent), and other types–had more wisdom, on average, than those in the three other groups. More importantly, it established for the first time that the link between meditation and wisdom might be attributable to a lower level of anxiety.“We are the first to show an association between wisdom, on the one hand, and mental and somatic practice, on the other,” Williams said. “We’re also the first to suggest that meditation’s ability to reduce everyday anxiety might partially explain this relationship.”Participants who practiced ballet had the lowest levels of wisdom. Nevertheless, the more they practiced ballet, the higher they scored on measures of psychological traits that are associated with wisdom.Causal relationship?Williams said it’s important to note that the research was not looking for and did not establish a causal relationship between wisdom and any of the four practices. But the results suggest that further study could identify such a causal relationship.“We hope our exploratory research will encourage others to replicate our results and look for other experiences that are linked with wisdom, as well as the factors that might explain such links,” Williams said.“Although wisdom, as an intellectual pursuit, is one of the oldest subjects studied by human-kind, it is one of the youngest, as a scientific pursuit,” he added.Ardelt thinks this study will generate a lot of interest with the public and in the growing field of the study of wisdom, especially due to the current interest in meditation. “These findings indicate that meditation might have more benefits than as a stress-reduction or pain-reduction technique,” she said.If mental and somatic practices can lead to more wisdom, “their applications should be explored across settings such as in the classroom or workplace with the goal of creating not only wiser people but also a wiser society,” the researchers concluded.
Pinterest LinkedIn Women performed better than men on the tests of both immediate recall and delayed recall among those showing evidence of minimal to moderate amounts of hippocampal shrinkage. At the high level of hippocampal shrinkage, there was no difference in the scores of men and women. At the score that indicates the start of verbal memory impairment, or 37 on a scale of zero to 75 for immediate recall, women showed greater evidence of hippocampal shrinkage (ratio of hippocampal volume to total brain volume multiplied by 103 was 5 compared to 6 for men).Mary Sano, PhD, of Icahn School of Medicine at Mount Sinai in New York, NY, and a member of the American Academy of Neurology, said in a corresponding editorial, “At a public policy level, the potential health care cost for under-detection or delayed diagnosis of women with Alzheimer’s disease or its early stages is staggering and should motivate funding in this area.”“If these results are confirmed, then we may need to adjust memory tests to account for the difference between men and women in order to improve our accuracy in diagnosis,” said Sundermann. Share on Twitter Share on Facebook Email Women may have a better memory for words than men despite evidence of similar levels of shrinkage in areas of the brain that show the earliest signs of Alzheimer’s disease, according to a study published in the March 16, 2016, online issue of Neurology®, the medical journal of the American Academy of Neurology.According to study author Erin E. Sundermann, PhD, of Albert Einstein College of Medicine in Bronx, NY, “One way to interpret the results is that because women have better verbal memory skills than men throughout life, women have a buffer of protection against loss of verbal memory before the effects of Alzheimer’s disease kick in. Because verbal memory tests are used to diagnose people with Alzheimer’s disease and its precursor, mild cognitive impairment, these tests may fail to detect mild cognitive impairment and Alzheimer’s disease in women until they are further along in the disease.”The study included participants from the Alzheimer’s Disease Neuroimaging Initiative: 235 people with Alzheimer’s disease, 694 people with mild cognitive impairment that included memory problems, and 379 people with no memory or thinking problems. The groups’ performance on a test of verbal memory was compared to the size of the hippocampal area of the brain, which is responsible for verbal memory and affected in the early stages of Alzheimer’s disease. Share
It is no surprise that a child prefers its mother’s voice to those of strangers. Beginning in the womb, a foetus’s developing auditory pathways sense the sounds and vibrations of its mother. Soon after birth, a child can identify its mother’s voice and will work to hear her voice better over unfamiliar female voices. A 2014 study of preterm infants showed that playing a recording of the mother’s voice when babies sucked on a pacifier was enough to improve development of oral feeding skills and shorten their hospital stay. A mother’s voice can soothe a child in stressful situations, reducing levels of cortisol, the stress hormone, and increasing levels of oxytocin, the social bonding hormone. Scientists have even traced the power of a mother’s voice to infants’ brains: a mother’s voice activates the anterior prefrontal cortex and the left posterior temporal region more strongly than an unfamiliar voice, priming the infant for the specialised task of speech processing.While it makes intuitive sense that a mother’s voice has special power over infants and toddlers, what happens as children grow up? Daniel Abrams, a neurobiologist at Stanford University School of Medicine, and his team of researchers set out to answer this question using functional MRI (fMRI), a neuroimaging technique that measures brain activity by detecting metabolic changes in blood flow. The researchers examined 24 children between the ages of seven and 12, who had normal IQs, had no development disorders, and were raised by their biological mothers. While in the MRI machine, these children listened to recordings of nonsense words spoken by their mothers or by other women. The researchers specifically chose nonsense words so as not to trigger brain circuits related to semantics. Regardless, the children were able to accurately identify their mother’s voice more than 97 per cent of the time in less than one second.But what actually happened when these older children heard their mother’s voice? The team hypothesised that listening to her voice would produce more activity in the so-called ‘voice-selective’ brain regions, involved in recognising voice and processing speech, compared with when they heard unfamiliar female voices. But what the scientists found was even more remarkable. A mother’s voice activated a wide range of brain structures including the amygdala, which regulates emotion, the nucleus accumbens and medial prefrontal cortex, which are part of a major reward circuit, and the fusiform face area, which processes visual face information. This pattern of brain activity can be likened to a neural fingerprint, where a mother’s voice triggers specific activity in her child’s brain. Share on Facebook LinkedIn Email Share on Twitter Pinterest Share The investigation didn’t stop there. The team found that the more neural connection between these ‘voice-selective’ brain regions and those related to mood, reward and face processing, the more social communication abilities a child had. In other words, the neural fingerprint of a mother’s voice within a child’s brain can predict that child’s ability to communicate in the social realm.If that neural fingerprint is thought of as a biomarker in a child’s brain, then how different does it look in children with disorders in social function, such as autism? And how does the neural fingerprint change in adolescence and into adulthood?The answers to these questions remain unknown, but it is now scientifically proven that most of us carry a mother’s voice in the neural patterns of our brain: bedtime stories, dinnertime conversation and the chatter we heard before birth identify us, uniquely, as surely as the fingerprint, enabling emotional development and social communication in childhood and, probably, through life.By Kate FehlhaberThis article was originally published at Aeon and has been republished under Creative Commons.
Share on Twitter Share on Facebook Matthew W. State, MD, PhD, the Oberndorf Family Distinguished Professor and chair of psychiatry at UCSF, first discovered the link between autism and SCN2A. According to State, who was not directly involved with the new study: “In autism research, understanding why mutations in a single gene can lead not only to ASDs, but to a wide range of other neurodevelopment disorders has emerged as a central question for the field. This new work provides critical clues that begin to unravel this mystery and could serve as a molecular ‘Rosetta Stone’ to illuminate autism pathology.”The study was published online January 26 in Biological Psychiatry.Genome sequencing points to SCN2A mutations as strongest known genetic drivers of autismThe advent of whole-exome genome sequencing and the amassing of large, well-defined study populations such as the Simons Simplex Collection (SSC) and the research cohorts assembled by the Autism Sequencing Consortium (ASC), have allowed researchers to make tremendous progress in recent years in identifying genetic risk factors for autism, said Sanders: “In the past four years we’ve gone from not really knowing how to find autism genes to having a long list of mutations linked to the disorder.”As a graduate student and postdoctoral researcher at Yale University working in State’s lab, Sanders led collaborations that searched for autism-linked genetic mutations by conducting large whole-exome genomic screens of more than 4,000 autistic children and their families participating in the SSC and ASC consortia. In studies published in 2012, 2014, and 2015, State, Sanders and collaborators found that de novo genetic mutations — spontaneous mutations not inherited from parents — play a role in the development of ASDs in at least 20 percent of all cases of autism, many more than previously recognized.These studies led to the identification of 65 genes with a strong likelihood of contributing to autism when mutated and implicated SCN2A as the human gene with the second strongest evidence for a causal role in driving ASDs. Analyses of additional SCN2A mutations In the current paper, confirm this result and elevate SCN2A to the single strongest case for a genetic driver of ASD.Autism-associated SCN2A mutations impede signaling in the developing brainSCN2A was in fact one of the first ASD-associated genes to be discovered. It encodes a sodium channel protein called NaV1.2 that is crucial to neurons’ ability to communicate electrically, especially during early brain development.In addition to its strong association with autism, SCN2A had also previously been implicated in epilepsy. When Sanders came to UCSF in 2015, he began collaborating with neurophysiologist Kevin Bender, PhD, an assistant professor of neurology and co-senior author of the study, to examine the mechanisms of how mutations SCN2A alter neuronal function to lead to these two different diseases.“Fortunately, the function of sodium channels is easy to test in the lab,” said Bender, who is also a member of UCSF’s Center for Integrative Neuroscience, Kavli Institute for Fundamental Neuroscience, and Weill Institute for Neurosciences. “Often you see mutations that are associated with a disease but you’re not really sure what the gene is supposed to do or how the mutations change its function. But neuroscientists have been studying sodium channels since the 1950s – the experiments are extremely clear.”Bender’s team measured how 12 SCN2A mutations observed in children with ASD affected the electrical properties of NaV1.2 channels in cultured human cells in the lab. As predicted, based on the mutations’ location on the protein, all 12 reduced the function of the sodium channel, but in a variety of different ways, ranging from stopping the channel from being made at all to simply blocking the pore through which sodium needs to flow for the channel to function.The researchers used this data to inform computer models of how the various channel mutations seen in children with ASD — as well as previously studied mutations seen in babies with infantile seizures — would impact the signaling properties of brain cells. They found that unlike mutations observed in patients with infantile seizures, which made model neurons more excitable, the mutations seen in children with ASD made it much harder for model neurons to send electrical signals.“It was remarkable to see how consistently neuronal function was disrupted by these different mutations seen in patients with autism,” said Roy Ben-Shalom, PhD, a post-doctoral researcher in the Bender lab who was lead author on the new paper. “The mutations all affected the channel in slightly different ways, but they ended up affecting neurons in almost exactly the same way.”Additional simulations of the effects of NaV1.2 defects on immature versus mature neurons indicated that autism-associated mutations would only have a major impact in the developing brain — since neurons transition away from relying on NaV1.2 channels as they mature — a finding consistent with the idea that the neurological changes that trigger in autism occur early in the womb or before one year of age, as previously proposed by Bender, Sanders and colleagues.SCN2A defects could be key to unlocking autism’s mysteriesThis study represents a first step in understanding how SCN2A mutations lead to autism and developmental delay, which the authors hope will both be immediately helpful to the families of patients with these mutations and also lead to better understanding of the mechanisms of ASD more generally.“These findings solidify SCN2A’s status as one of the most important genes in autism,” Bender said. “They give us a place to start exploring exactly how changes in early brain development lead to this condition.”A key next step, the researchers say, is understanding whether the severity of autism and developmental delay can be predicted by the specific SCN2A mutation a patient has, research that will require close collaboration between scientists and families affected by these mutations. An active SCN2A patient group is helping to coordinate this via the website http://www.scn2a.org in collaboration with SFARI, which provided major funding for the new study (SFARI 362242) alongside grants from the US National Institutes of Health (NINDS, NIMH).The new study is a perfect example of the power of the cross-disciplinary mindset of the new UCSF Weill Institute for Neuroscience, Sanders said: “Kevin and I came at this question from completely different angles – from genetics and from neurophysiology. When you bring people together from different backgrounds, as the Weill Institute does, you end up finding stories like this: a result as clear as night and day, but one we never would have seen without this collaboration.” LinkedIn Email Share Distinct sets of genetic defects in a single neuronal protein can lead either to infantile epilepsy or to autism spectrum disorders (ASDs), depending on whether the respective mutations boost the protein’s function or sabotage it, according to a new study by UC San Francisco researchers. Tracing how these particular genetic defects lead to more general changes in brain function could unlock fundamental mysteries about how events early in brain development lead to autism, the authors say.“The genetics of neuropsychiatric disease is often complicated, but here we have a single gene in which specific mutations can cause either infantile seizures or autism in a consistent and predictable manner,” said Stephan Sanders, MD, PhD, an assistant professor of psychiatry at UCSF and member of the UCSF Weill Institute for Neurosciences who is co-senior author of the new study. “This gives us an opportunity to understand both what these disorders have in common and what makes them different.”The findings are a first step towards understanding how different subtle changes in neural function in utero could lead to the development of either a seizure-prone brain or an autistic brain in infancy, the authors say. The study also further implicates the gene responsible for these changes — called SCN2A — as the single human gene with the strongest evidence for a causal role in driving ASDs. Pinterest
Share Pinterest “We know that cholinesterase inhibitors can make a difference for Alzheimer’s patients, so we wanted to find out if we could identify patients at risk for Alzheimer’s who might also benefit from this treatment,” said D.P. Devanand, MBBS, MD, professor of psychiatry, scientist in the Gertrude H. Sergievsky Center at CUMC, and co-director of the Memory Disorders Clinic and the Late Life Depression Clinic at NYSPI. “Since odor identification tests have been shown to predict progression to Alzheimer’s, we hypothesized that these tests would also allow us to discover which patients with MCI would be more likely to improve with donepezil treatment.”In this year-long study, 37 participants with MCI underwent odor identification testing with the University of Pennsylvania Smell Identification Test (UPSIT). The test was administered before and after using an atropine nasal spray that blocks cholinergic transmission.The patients were then treated with donepezil for 52 weeks, and were periodically reevaluated with the UPSIT and with memory and cognitive function tests. Those who had a greater decline in UPSIT scores, indicating greater cholinergic deficits in the brain, after using the anticholinergic nasal spray test saw greater cognitive improvement with donepezil.In addition, short-term improvement in odor identification from baseline to eight weeks tended to predict longer-term cognitive improvement with donepezil treatment over one year.“These results, particularly if replicated in larger populations, suggest that these simple inexpensive strategies have the potential to improve the selection of patients with mild cognitive impairment who are likely to benefit from treatment with cholinesterase inhibitors like donepezil,” said Dr. Devanand. LinkedIn Researchers at Columbia University Medical Center (CUMC) and the New York State Psychiatric Institute (NYSPI) may have discovered a way to use a patient’s sense of smell to treat Alzheimer’s disease before it ever develops. Having an impaired sense of smell is recognized as one of the early signs of cognitive decline, before the clinical onset of Alzheimer’s disease. The researchers at CUMC and NYSPI have found a way to use that effect to determine if patients with mild cognitive impairment may respond to cholinesterase inhibitor drugs to treat Alzheimer’s disease.The findings were published online this week in the Journal of Alzheimer’s Disease.Cholinesterase inhibitors, such as donepezil, enhance cholinergic function by increasing the transmission of the neurotransmitter acetylcholine in the brain. Cholinergic function is impaired in individuals with Alzheimer’s disease. Cholinesterase inhibitors, which block an enzyme that breaks down acetylcholine, have shown some effectiveness in improving the cognitive symptoms of Alzheimer’s disease. However, they have not been proven effective as a treatment for individuals with mild cognitive impairment (MCI), a condition that markedly increases the risk of Alzheimer’s disease. Email Share on Facebook Share on Twitter