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News Article | May 11, 2017
Site: www.eurekalert.org

BOSTON - Brucellosis is an infectious disease of livestock that may be transmitted to farm workers or consumers of unpasteurized dairy products. Easy to spread and hard to detect, the bacteria that cause the illness, Brucella species, are considered potential bioterror weapons. Yet, precisely because Brucella species are so dangerous to handle, research on this important disease-causing agent, or pathogen, has lagged behind that of other infectious diseases. Using an innovative method they developed to study the infectious process, investigators at Beth Israel Deaconess Medical Center (BIDMC) established a safer way to study Brucella. In an early test of the model, the research team observed a surprising and previously undocumented interaction during the infectious process. The presence of another pathogen appeared to improve the infectious potential of Brucella. The report was published in the journal Infection and Immunity. "Our toolkit is simple, versatile and applicable to any type of pathogen," said James Kirby, MD, Director of the Clinical Microbiology Laboratory at BIDMC and Associate Professor of Pathology at Harvard Medical School. "This will be something that will help the scientific community study infectious disease more efficiently going forward because bacterial strains of interest can be constructed so easily, saving a lot of time and effort." Kirby and co-author Yoon-Suk Kang, PhD, a post-doctoral fellow in Kirby's lab used their technique to engineer a special strain of Brucella designed to emit colored light so they could more easily observe it infect host cells the lab. Common in goats, sheep, cattle, pigs and dogs, the four Brucella species capable of infecting humans are classified as potential biothreat organisms that must be studied in designated biosafety level 3 laboratories specially equipped to contain them. But Kirby and Kang, used another Brucella species, B. neotomae - known to infect only rodents - to see if it had enough in common with its more dangerous relatives to serve as a safer-to-handle investigational model for all Brucella species. While observing their custom strain, Kirby and Kang witnessed an unprecedented interaction between B. neotomae and Legionella pneumophila, the pathogen that causes Legionnaires' disease in humans. In addition to emitting light, the genetically-altered strain of B. neotomae was also designed to lack the physical structure it needs - a molecular syringe - to attack host cells. On their own, these engineered bacteria can't grow and multiply inside the host cell. However, when the host cells were co-infected with this strain of Brucella and L. pneumophila - also engineered to emit colored light - at the same time, the harmless B. neotomae thrived. In fact, Kirby notes this de-fanged version of B. neotomae grew better in the presence of L. pneumophila than virulent Brucella normally does without it. "Legionella provided all the factors Brucella needs for infection," said Kirby. "It was completely out of the blue. It highlights that pathogens can interact in unexpected ways. The whole is greater than the sum of its parts." The researchers' new technique creates the light-emitting bacteria by introducing genes for fluorescent proteins into their genomes. The concept itself is not new, but the genetic "tool kit" developed by Kirby and Kang greatly streamlines the process by using easy-to-manipulate genes called transposons - sometimes called jumping genes - to quickly and safely label the bacteria. Kirby and Kang's technique avoids one significant drawback to traditional means of labeling bacteria for study. Typically, scientists isolate bacteria for study by engineering drug-resistant strains and growing them in a petri dish infused with antibiotics, which will kill any bacteria not relevant to the experiment. "That's something we've been concerned about," said Kirby, whose lab also seeks to develop novel antimicrobials as drug-resistant bacteria become an increasing problem globally. "We don't want to make bacteria more resistant to antibiotics. Our toolkit won't confer resistance to anything that might be used in human therapy." This work was supported by grants to Kirby from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, under award numbers R01AI099122, R21AI112694 and R21AI076691. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .


Contact Information: Enrica Ardemagni, President eardemagni@ncihc.org April 18, 2017 Shari Gold-Gomez recognized as Language Access Champion for Interpreter Services at BIDMC Washington, D.C.


News Article | May 8, 2017
Site: www.eurekalert.org

New research from Boston Children's Hospital and Beth Israel Deaconess Medical Center (BIDMC) shows that chronic sleep loss increases pain sensitivity. It suggests that chronic pain sufferers can get relief by getting more sleep, or, short of that, taking medications to promote wakefulness such as caffeine. Both approaches performed better than standard analgesics in a rigorous study in mice, described in the May 8, 2017 issue of Nature Medicine. Pain physiologist Alban Latremoliere, PhD, of Boston Children's and sleep physiologist Chloe Alexandre, PhD, of BIDMC precisely measured the effects of acute or chronic sleep loss on sleepiness and sensitivity to both painful and non-painful stimuli. They then tested standard pain medications, like ibuprofen and morphine, as well as wakefulness-promoting agents like caffeine and modafinil. Their findings reveal an unexpected role for alertness in setting pain sensitivity. The team started by measuring normal sleep cycles, using tiny headsets that took electroencephalography (EEG) and electromyography (EMG) readings. "For each mouse, we have exact baseline data on how much they sleep and what their sensory sensitivity is," says Latremoliere, who works in the lab of Clifford Woolf, PhD, in the F.M. Kirby Neurobiology Center at Boston Children's. Next, unlike other sleep studies that force mice to stay awake walking treadmills or falling from platforms, Alexandre, Latremoliere and colleagues deprived mice of sleep in a way that mimics what happens with people: They entertained them. "We developed a protocol to chronically sleep-deprive mice in a non-stressful manner, by providing them with toys and activities at the time they were supposed to go to sleep, thereby extending the wake period," says Alexandre, who works in the lab of Thomas Scammell, MD, at BIDMC. "This is similar to what most of us do when we stay awake a little bit too much watching late-night TV each weekday." To keep the mice awake, researchers kept vigil, providing the mice with custom-made toys as interest flagged while being careful not to overstimulate them. "Mice love nesting, so when they started to get sleepy (as seen by their EEG/EMG pattern) we would give them nesting materials like a wipe or cotton ball," says Latremoliere. "Rodents also like chewing, so we introduced a lot of activities based around chewing, for example, having to chew through something to get to a cotton ball." In this way, they kept groups of six to 12 mice awake for as long as 12 hours in one session, or six hours for five consecutive days, monitoring sleepiness and stress hormones (to make sure they weren't stressed) and testing for pain along the way. Pain sensitivity was measured in a blinded fashion by exposing mice to controlled amounts of heat, cold, pressure or capsaicin (the agent in hot chili peppers) and then measuring how long it took the animal to move away (or lick away the discomfort caused by capsaicin). The researchers also tested responses to non-painful stimuli, such as jumping when startled by a sudden loud sound. "We found that five consecutive days of moderate sleep deprivation can significantly exacerbate pain sensitivity over time in otherwise healthy mice," says Alexandre. "The response was specific to pain, and was not due to a state of general hyperexcitability to any stimuli." Surprisingly, common analgesics like ibuprofen did not block sleep-loss-induced pain hypersensitivity. Even morphine lost most of its efficacy in sleep-deprived mice. These observations suggest that patients using these drugs for pain relief might have to increase their dose to compensate for lost efficacy due to sleep loss, thereby increasing their risk for side effects. In contrast, both caffeine and modafinil, drugs used to promote wakefulness, successfully blocked the pain hypersensitivity caused by both acute and chronic sleep loss. Interestingly, in non-sleep-deprived mice, these compounds had no analgesic properties. "This represents a new kind of analgesic that hadn't been considered before, one that depends on the biological state of the animal," says Woolf, director of the Kirby Center at Boston Children's. "Such drugs could help disrupt the chronic pain cycle, in which pain disrupts sleep, which then promotes pain, which further disrupts sleep." The researchers conclude that rather than just taking painkillers, patients with chronic pain might benefit from better sleep habits or sleep-promoting medications at night, coupled with daytime alertness-promoting agents to try to break the pain cycle. Some painkillers already include caffeine as an ingredient, although its mechanism of action isn't yet known. Both caffeine and modafinil boost dopamine circuits in the brain, so that may provide a clue. "This work was supported by a novel NIH program that required a pain scientist to join a non-pain scientist to tackle a completely new area of research," notes Scammel, professor of neurology at BIDMC. "This cross-disciplinary collaboration enabled our labs to discover unsuspected links between sleep and pain with actionable clinical implications for improving pain management." "Many patients with chronic pain suffer from poor sleep and daytime fatigue, and some pain medications themselves can contribute to these co-morbidities," notes Kiran Maski, MD, a specialist in sleep disorders at Boston Children's. "This study suggests a novel approach to pain management that would be relatively easy to implement in clinical care. Clinical research is needed to understand what sleep duration is required and to test the efficacy of wake-promoting medications in chronic pain patients." Alexandre (BIDMC) and Latremoliere (Boston Children's) were co-first authors on the paper. Woolf (Boston Children's) and Scammell (BIDMC) were co-senior authors. Ashley Ferreira and Giulia Miracca of Boston Children's and Mihoko Yamamoto of BIDMC were coauthors. This work was supported by grants from the NIH (R01DE022912, R01NS038253). The Neurodevelopmental Behavior and Pharmacokinetics Cores at Boston Children's Hospital, the metabolic Physiology Core at BIDMC (P30DK057521) and P01HL09491 also supported this study. Boston Children's Hospital is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including seven members of the National Academy of Sciences, 11 members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's today is a 404-bed comprehensive center for pediatric and adolescent health care. Boston Children's is also the primary pediatric teaching affiliate of Harvard Medical School. For more, visit our Vector and Thriving blogs and follow us on our social media channels @BostonChildrens, @BCH_Innovation, Facebook and YouTube. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .


News Article | February 1, 2017
Site: www.techtimes.com

Beth Israel Deaconess Medical Center (BIDMC) and Lahey Health have announced they will try, for the fourth time, to combine their forces and create one single entity, as an attempt to better compete with Partners HealthCare. The system would be led by Dr. Kevin Tabb, who is the current CEO of Beth Israel Deaconess Medical Center. It is the fourth time in the past six years that these two major systems are trying to merge. Should this attempt be successful, the system will be the largest hospital merger in Massachusetts since the mid-1990s. "We are engaged in ongoing discussions, exploring the opportunity to combine our two systems and create the region's premier integrated health care delivery system, one that would offer patients exceptional care and unparalleled value, while keeping care in the community whenever possible," noted Tabb in a statement. According to the administrators of the two systems, the networks have complementary advantages and should work well together. While Lahey has one of the biggest behavioral health divisions in the United States and a hospice program, BIDMC is more focused on research and teaching. As SVP and general counsel for BIDMC, Jamie Katz believes that once the two networks are united, it will be able to offer a full range of services in complementary geographic areas. What these both systems have in common is their positioning statement on the market. Their official declaration is that they deliver qualitative services that can compete with Partners HealthCare, the largest system in the state, but at lower prices. However, not everybody is as optimistic about this possible union as the administrators of the two health care providers, especially since there is no guarantee that the overall decrease in the administrative costs will stop the leaders of the union from charging more for their services. "Every merger means fewer competitors and more leverage for the parties that merge to squeeze higher prices and premiums out of everybody who lives or works or does business in Massachusetts," noted Alan Sager, a professor of health law, policy and management at the Boston University School of Public Health. When the affiliation of Partners HealthCare was created, Beth Israel was invited to be part of it. However, the company refused and partnered with Deaconess-Hospital, hoping that it will create the necessary leverage for a close competition on the market. As sources report, this initial merge wasn't a very successful one from the start, partly because of the major differences in the vision of the two hospitals. The first time the information was made public concerning a possible union between Beth Israel and Lahey was in 2011 when a deal fell through. Both the systems were interested in building their own network to compete against the Partners, and a union would have made sense. In 2014, a merger of the two systems with Atrius Health was made public. Although geographically speaking it made sense, due to the different areas the companies covered, the merger never happened. Then, in October 2015, another attempt failed yet again. Despite the efforts, the two entities were not able to unite the first three times. Should they go through with the merger this time, the health care system would undergo a significant change. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.


News Article | February 17, 2017
Site: www.eurekalert.org

BOSTON - A new study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) has found that lower levels of vitamin D in the blood increase the risk of clinical relapse in patients with Ulcerative Colitis (UC), an inflammatory bowel disease that causes long-lasting inflammation and ulcers in the colon. The study was published in the February issue of the journal Clinical Gastroenterology and Hepatology. Lower vitamin D levels have been associated with active disease in patients with UC, but it has been unknown whether they increase disease relapses. "Prior studies in patients with Crohn's disease and Ulcerative Colitis had linked low vitamin D levels to disease flare-ups," said senior author Alan Moss, MD, a gastroenterologist at the Digestive Disease Center at BIDMC and Associate Professor of Medicine at Harvard Medical School. "However, it has been unclear if the flare-up was lowering vitamin D levels, or if low vitamin D levels were causing the flare-up. We thought that if we looked at vitamin D levels when the disease was inactive and then followed patients moving forward, the impact of baseline vitamin D levels on future events may be clearer." Moss and colleagues collected vitamin D serum levels through a physician-blinded prospective study of 70 patients with UC in clinical remission who were followed up after a surveillance colonoscopy at BIDMC. The study measured vitamin D levels in blood samples and levels of inflammation through blood tests and biopsies. The researchers then followed the patients for 12 months and compared the data from participating patients who remained well and the others who experienced relapses. The investigators found the mean baseline vitamin D level to be lower in patients who later relapsed than those who did not. "Patients who had higher vitamin D levels when their disease was in remission were less likely to experience a relapse in the future," said John Gubatan, MD, a physician at BIDMC and first author of the study. "This suggests that higher vitamin D levels may play some role in preventing the UC relapse." The threshold level of blood vitamin D that was protective was greater than 35ng/ml, which is within the range recommended by the National Institutes of Health for a healthy individual. Ongoing work by Gubatan and Moss is now examining the link between vitamin D and a protein called cathelicidin in the cells lining the colon. The link may have beneficial effects on microbial composition, an important component of a healthy colon. Building on this research, investigators are trying to unravel how vitamin D may protect cells in the colon and the microbial composition of the bacteria, fungi, protozoa and viruses that live on and inside the human body, Moss noted. In addition to Moss and Gubatan, the study was performed at BIDMC by authors Shuji Mitsuhashi, Talia Zenlea, MD, Laura Rosenberg, MD, and Simon Robson, MB, ChB, FRCP, PhD. This work was supported by grants from the National Institutes of Health (K23DK084338) and a Rabb Research Award (ACM). Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .


News Article | December 26, 2016
Site: www.eurekalert.org

BOSTON - Scientific research over the past decade has concentrated almost exclusively on the 2 percent of the genome's protein coding regions, virtually ignoring the other 98 percent, a vast universe of non-coding genetic material previously dismissed as nothing more than 'junk.' Now, a team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) reveals that one type -- called long non-coding RNA (lncRNA) -- may be critically important for controlling cellular components in a tissue-specific manner. Published online today in the journal Nature, the new research points to an lncRNA's key role in helping control processes related to muscle regeneration and cancer. Long non-coding RNAs appear to be transcribed from our DNA in a similar manner to coding messenger RNAs but are not translated into proteins. While lncRNA molecules do not produce correspondingly lengthy proteins, researchers have wondered whether some of these molecules may contain segments of sequences that can code for very short proteins, or polypeptides. "Whether such small, hidden polypeptides are actually functional, or represent 'translational noise' within the cell is still relatively unclear," said senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center and Cancer Research Institute at BIDMC. "Our team set about trying to understand to what extent lncRNA molecules might actually encode functional polypeptides, and how important such peptides might be." The investigators used computational analyses to predict potential polypeptides that could be encoded by known lncRNA molecules, and then they used mass spectrometry to determine if these putative polypeptides were actually expressed. "With this approach we actually identified many expressed hidden polypeptides and went on to characterize one in particular," Pandolfi explained. This specific lncRNA molecule is termed LINC00961 and encodes a 90 amino acid polypeptide. A variety of molecular and biochemical experiments revealed that the LINC00961 encoded polypeptide played an important role in modulating the activity of the mTORC1 protein complex, which is a critical sensor of nutrient availability within cells. The complex also regulates a variety of cellular processes including translation, metabolism, cell growth, and proliferation, and alterations in its function can lead to diseases such as cancer. Because the LINC00961 polypeptide appeared to specifically block mTORC1's ability to sense stimulation with amino acids, the investigators named the peptide encoded by the lncRNA SPAR (Small regulatory Polypeptide of Amino acid Response). Pandolfi and his team found that the SPAR encoding lncRNA is highly expressed in a number of tissue types, including muscle. Experiments conducted in mice demonstrated that through its effects on mTORC1, the SPAR polypeptide helps regulate the muscle's ability to regenerate and repair after injury. Specifically, expression of LINC00961 is blocked following muscle injury in mice, leading to reduced levels of SPAR and maximal mTORC1 activity to promote tissue regeneration. "The experimental approach we used allowed us to eliminate expression of the SPAR polypeptide, while maintaining expression of the host lncRNA," said lead author Akinobu Matsumoto, PhD, research fellow at the Cancer Center at BIDMC and lead author of the study. "We are able to ascribe this function to the coding function of the lncRNA rather than any non-coding function it may also have." The findings suggest that therapeutic strategies that restrict expression of SPAR in injured muscle may promote a more rapid regeneration of tissue. The results suggest that lncRNAs may have diverse roles and functions. Although they may not code for large proteins, lncRNAs may produce small polypeptides that can fine tune the activity of critical cellular components. The findings also expand the repertoire of peptide-coding genes in the human genome that should be studied and annotated. The study also provides insights on how mTORC1 activity may be attuned to meet the distinct needs of a specific tissue. "An ability to target such modulators could be of great advantage from a therapeutic perspective, allowing for control of mTORC1 activity in cells or tissues that express such modulators while not affecting its activity and function in other tissue and cell types," explained co-author John Clohessy, PhD, Instructor in Medicine at BIDMC and a senior member of Pandolfi's research team. Indeed, a key feature of many lncRNAs is that their expression is often highly tissue-specific. Thus, targeting small polypeptides encoded by lncRNA molecules may provide the key to regulating common cellular components in a tissue-specific manner. Because the mTORC1 complex is frequently deregulated in conditions such as cancer, the research team is now seeking to determine if SPAR can influence additional cellular functions of mTORC1 that might be involved in different diseases. "We are very excited about this discovery," said Pandolfi. "It represents a new and startling mechanism by which important sensory pathways can be regulated within cells, and we believe it will have important implications for how we approach the design of therapies and treatments in the future." Study coauthors include BIDMC investigators Akinobu Matsumoto, Alessandra Pasut, Jacqueline Fung, Emanuele Monteleone, and John G. Clohessy. Other co-investigators include Masaki Matsumoto and Keiichi I. Nakayama of Kyushu University, Riu Yamashita of Tohoku University, and Alan Saghatelian of the Salk Institute for Biological Studies. This work was supported in part by the National Institutes of Health grants R01 CA082328 and R35 CA197529. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .


News Article | February 22, 2017
Site: www.eurekalert.org

BOSTON - Sleep remains an enduring biological mystery with major clinical relevance, according to a review by clinician-researcher Thomas Scammell, MD, of Beth Israel Deaconess Medical Center (BIDMC) and colleagues. In recent decades, new technologies have allowed neuroscientists to identify multiple brain circuits that govern the sleep/wake cycle, as well as the factors that can influence it, such as caffeine and light. But the brain's complexity is still a stumbling block in understanding this ubiquitous and necessary animal behavior, the researchers wrote. Their review appeared today in the journal Neuron. "In the last ten years, neuroscientists have had access to new tools with which we can test the roles of very specific neurons in the brain," said lead author Scammell, a professor in the department of neurology at BIDMC. "When we know the specific relevant players in the brain, it allows us to develop therapies to help people get to sleep or help sleepy people be more alert during the day." Specifically, two technologies developed since 2000 allow neurologists to switch specific neurons on or off. In a process called chemogenetics, researchers use drugs that have an effect only in a genetically-defined group of cells to determine the neurons' role. Optogenetics uses laser light to turn on or turn off targeted brain cells. These techniques have revealed which neuronal circuits promote wakefulness and sleep throughout the brain, especially in the brain stem and the hypothalamus. "We can now interrogate neurons in a more precise way," said Scammell. "The techniques are very similar, but optogenetics works over a short time scale, on the order of seconds. With chemogenetics, we can watch over several hours what happens when we turn certain neurons on or off." Sleep researchers have also made important discoveries about the fundamental chemistry of sleepiness in recent years. In a major breakthrough in the late 1990s, scientists discovered a previously unknown chemical, a neurotransmitter called orexin, required for maintaining long periods of wakefulness. The loss of orexin production causes the common sleep disorder narcolepsy, which is characterized by chronic sleepiness and irregular REM sleep. Today, pharmaceutical companies make drugs that intentionally block the orexin system to treat insomnia. Researchers are also trying to develop drugs that mimic orexin to wake people up. "A drug that acts like orexin could be as great for patients with narcolepsy as insulin is for people with diabetes," said Scammell. Neuroscience research has also revealed the brain circuity governing circadian rhythms, the biological clock that synchronizes sleepiness and wakefulness with night and day. Located deep in the hypothalamus, the suprachiasmatic nucleus (SCN) regulates circadian rhythms and is capable of maintaining them for some time even in total darkness. However, the SCN is no match for the social norms surrounding people's sleep habits. "People increasingly use their electronic devices in bed, which tricks the brain into thinking it's being exposed to daylight," said Scammell. "The internal clock gets reset, making it much harder to wake up in the morning." Phones and tablets are just one of the reasons about a third of all American adults are sleep deprived, getting much less than the recommended seven to eight hours of sleep per night. That raises more questions about why some people need more or less than that, and why some people can tolerate a sleep deficit so much better than others. The links among lack of sleep or poor sleep and metabolic disease, cancer risk and mood disorders also require further study. With each of the brain's hundreds of thousands of neurons networked to each other, scientists will need a deeper knowledge of the brain's inner workings to understand how the circuits that regulate sleep interact. "There's tremendous dialog back and forth among these circuits," said Scammell, who notes today's technology allows scientists to monitor dozens of neurons at a time within one region of the brain. "Our ability to record activity in just a handful of neurons simultaneously is still not anything close to understanding the whole brain, but at least it's a step in the right direction." Study co-authors include: Elda Arrigoni, PhD, of BIDMC and Jonathan O. Lipton, MD, PhD, of Boston Children's Hospital. The work was supported by the National Institutes of Health (HL095491, DE022912, NS091126, and HD071026. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .


News Article | December 19, 2016
Site: www.eurekalert.org

BOSTON - Neuroscientists at Beth Israel Deaconess Medical Center (BIDMC) have mapped the brain injuries - or lesions - that result in delusional misidentification syndromes (DMS), a group of rare disorders that leaves patients convinced people and places aren't really as they seem. In a study published in the journal Brain, Michael D. Fox, MD, PhD, Director of the Laboratory for Brain Network Imaging and Modulation and the Associate Director of the Berenson-Allen Center for Noninvasive Brain Stimulation at BIDMC and colleagues reveal the neuro-anatomy underlying these syndromes for the first time. "How the brain generates complex symptoms like this has long been a mystery," said Fox. "We showed how complex symptoms can emerge based on brain connectivity. With a lesion in exactly the right place, you can disrupt the brain's familiarity detector and reality monitor simultaneously, resulting in bizarre delusions. Understanding where these symptoms come from is an important step toward treating them." Delusional misidentification syndromes are among the most striking and least understood disorders encountered in neurology and psychiatry. First documented nearly a century ago, Capgras syndrome is a rare disorder in which patients recognize a family member while simultaneously experiencing that person as unfamiliar, leading to the conclusion that an imposter is impersonating their loved one. Conversely, the Fregoli delusion is the belief that strangers are actually loved ones in disguise. Misidentification delusions can also apply to pets and places. Fox and colleagues, including lead author R. Ryan Darby, MD, the Sidney R. Baer, Jr. Foundational Fellow in the Clinical Neurosciences at the Berenson-Allen Center at BIDMC, identified 17 patients with delusional misidentification syndromes and mapped them onto a standardized brain atlas. Then, using the lesion network mapping technique they recently developed, Darby and colleagues determined that all 17 lesions were functionally connected to an area of the brain called the retrosplenial cortex - thought to be involved in perceiving familiarity. Sixteen of the 17 lesions were also connected to a region in the right ventral frontal cortex, associated with belief evaluation. The scientists compared the data to 15 control brain injuries that led to delusions other than misidentification delusions. "Lesions causing all types of delusions were connected to belief violation regions, suggesting that these regions are involved in monitoring for delusional beliefs in general," Darby said. "However, only lesions causing delusional misidentifications were connected to familiarity regions, explaining the specific bizarre content - abnormal feelings of familiarity - in these delusions. In other words, lesions had to be connected to both regions to develop delusions like Capgras." The scientists note that their network mapping technique does not involve obtaining functional neuroimaging (fMRI) from the patients studied. Rather, data from normal patients determines which regions of the brain are normally connected to the mapped lesion locations. While this methodology carries several advantages, it does not prove these two regions are dysfunctional in delusional patients following the lesion. Doing so would require recruiting a large number of patients with the rare disorder to a follow up study, noted Darby. However, the new information gleaned from their study may help patients' families cope with a loved one's misidentification delusions -- which sometimes disappear as mysteriously as they come on. "The impact on the patient's family can be heart-breaking," said Darby. "I've seen patients who, thinking their homes were replicas, would pack their bags every night, hoping to return to their 'real' home. Patients who believe a spouse is an imposter often lose intimacy. In these cases, even just knowing that the delusion has a name and is part of a neurological disorder can be helpful for family members." Study coauthors include Simon Laganiere, MD, and Alvaro Pascual-Leone, MD, PhD, of the Berenson-Allen Center for Noninvasive Brain Stimulation at BIDMC; and Sashank Prasad, MD, of the Department of Neurology at Brigham and Women's Hospital. This work was supported by funding from the Sidney R. Baer, Jr. Foundation; grants from the National Institutes of Health (R01HD069776, R01NS073601, R21 NS082870, R21 MH099196, R21 NS085491, R21 HD07616, R25NS065743, K23NS083741); the Football Players Health Study at Harvard University; Harvard Catalyst | The Harvard Clinical and Translational Science Center (NCRR and the NCATS NIH, UL1 RR025758), and the American Brain Foundation. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .


News Article | February 21, 2017
Site: www.eurekalert.org

In less than one year, researchers have developed multiple vaccine platforms that provide robust protection against Zika virus challenge in animal models BOSTON - As public health officials warn that spring's warmer temperatures may herald another increase of Zika virus infections in the Caribbean and North and South America, researchers around the world are racing to develop safe and effective measures to prevent the disease. In a review paper published today in the journal Immunity, a group of leading vaccine scientists -- including Dan H. Barouch, MD, PhD, of Beth Israel Deaconess Medical Center (BIDMC) -- outline advances in the hunt for a Zika vaccine and the challenges that still lie ahead. "The pace of preclinical and early clinical development for Zika vaccines is unprecedented," said Barouch, corresponding author and director of the Center for Virology and Vaccine Research at BIDMC. "In less than a year, our group and others have demonstrated that multiple vaccine platforms can provide robust protection against Zika virus challenge in animal models. However, unique challenges will need to be addressed in the clinical development of a Zika vaccine. " The recent outbreak of the Zika virus in the Americas began in Brazil nearly two years ago. By February 2016, the World Health Organization had declared the epidemic a global public health emergency, based largely on the virus' newly-established link to microcephaly and other major birth defects in babies born to infected mothers. The virus has also been associated with the neurologic disorder Guillain-Barré syndrome in adults. In a previously published paper, Barouch and colleagues, including Colonel Nelson L. Michael, MD, PhD, director of the Military HIV Research Program at the Walter Reed Army Institute of Research (WRAIR) and Stephen Thomas, MD, Upstate Medical University, State University of New York, demonstrated that three different vaccine candidates provided robust protection against Zika virus in both mice and rhesus monkeys. Several human clinical trials began last fall at test sites including BIDMC, WRAIR, and National Institute of Allergy and Infectious Diseases affiliated clinical trial sites. "The rapid advancement of Zika vaccine candidates into clinical trials reflects the uniquely focused and effective collaboration among scientists in the field to address this important global problem," said Barouch. Despite the accelerated pace of research, much remains unknown about the virus, raising unique challenges in developing a vaccine. Safety considerations are especially critical, given that the target population for a Zika vaccine would likely include men and women of childbearing age. Zika is a member of the flavivirus family of viruses, which includes West Nile virus, yellow fever virus, and dengue viruses, for which successful vaccines have been developed. Studies suggest that Zika-induced antibody responses may also cross-react with other flaviviruses, particularly dengue virus. Whether or not this antibody cross-reactivity may have clinical consequences is another consideration for Zika vaccines and requires further study. Co-authors include: Stephen J. Thomas, MD, Upstate Medical University, State University of New York, Syracuse; and Colonel Nelson L. Michael, MD, PhD, director, Military HIV Research Program, at Walter Reed Army Institute of Research (WRAIR). The review's authors acknowledge support from the U.S. Military Research and Material Command and the U.S. Military HIV Research Program; the National Institutes of Health (AI095985, AI096040, AI100663, AI124377); and the Ragon Institute of MGH, MIT, and Harvard. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .


Triple-negative breast cancer quickly becomes resistant to current therapies, leaving patients no therapeutic options. BIDMC researchers discovered that TNBC cells increase production of pyrimidine nucleotides in response to traditional chemotherapy. Discovery represents a vulnerability that can be exploited by blocking pyrimidine using an existing inhibitor in combination with chemotherapy.

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