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6 ways you can prepare to “age well”strength trainingYou're probably already doing a lot to ensure that you stay in good health and are able to enjoy your later years: eating right, exercising, getting checkups and screenings as recommended by your doctor. But it also makes sense to have some contingency plans for the bumps in the road that might occur.Living Better, Living Longer Adapt your home. Stairs, baths, and kitchens can present hazards for older people. Even if you don't need to make changes now, do an annual safety review so you can make necessary updates if your needs change.Prevent falls. Falls are a big deal for older people — they often result in fractures that can lead to disability, further health problems, or even death. Safety precautions are important, but so are exercises that can improve balance and strength.Consider your housing options. You might consider investigating naturally occurring retirement communities (NORCs). These neighborhoods and housing complexes aren't developed specifically to serve seniors — and, in fact, tend to host a mix of ages — but because they have plenty of coordinated care and support available, they are senior-friendly.Think ahead about how to get the help you may need. Meal preparation, transportation, home repair, housecleaning, and help with financial tasks such as paying bills might be hired out if you can afford it, or shared among friends and family. Elder services offered in your community might be another option.Plan for emergencies. Who would you call in an emergency? Is there someone who can check in on you regularly? What would you do if you fell and couldn't reach the phone? Keep emergency numbers near each phone or on speed dial. Carry a cellphone (preferably with large buttons and a bright screen), or consider investing in some type of personal alarm system.Write advance care directives. Advance care directives, such as a living will, durable power of attorney for health care, and health care proxy, allow you to explain the type of medical care you want if you're too sick, confused, or injured to voice your wishes. Every adult should have these documents.To learn more ways to enjoy independence and good health in your senior years, buy Living Better, Living Longer, a Special Health Report from Harvard Medical School.
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Calcium, vitamin D, and fracturesPOSTED FEBRUARY 12, 2018, 10:30 AM , UPDATED FEBRUARY 22, 2018. Monique Tello, MD, MPHMonique Tello, MD, MPHContributing EditorWhen I saw the headlines about this recently published study on bone health saying “Vitamin D and calcium supplements may not lower fracture risk.” I thought: Wait, that’s news? I think I remember seeing that headline a few years ago.Indeed, in 2015, this very blog reported on similar studies of calcium supplements, noting that calcium supplements have risks and side effects, and are not likely indicated for most healthy community-dwelling adults over 50. These folks are not in a high-risk category for vitamin deficiencies, osteoporosis, and fractures, and we usually advise them to get their calcium from food. Dietary sources of calcium are everywhere, including milk and yogurt, but also include green leafy veggies like collard greens, legumes like black-eyed peas, tofu, almonds, orange juice… the list goes on (and you can check it out here).What’s new with this most recent study?This research found that taking vitamin D supplements did not protect against fractures in people over 50. The authors examined 33 research studies including over 50, 000 people for their analysis. However, and it’s a big however, study investigators note several times that their research included only healthy people out in the community, and that their findings do not apply to elderly people living in nursing homes who may have a poorer diet, less sun exposure and mobility, and who are at particularly high risk for fractures. Indeed, the original recommendations for calcium supplementation were based on a study of elderly, nursing-home bound women with vitamin deficiencies and low bone density, for whom calcium and vitamin D supplements did significantly reduce fracture risk.What is the takeaway?Well, simply, not much has changed. My advice to my healthy patients is still to get calcium from foods, and the best diet for this is a Mediterranean-style diet rich in colorful plants, plenty of legumes, and fish. This plus high-protein, low-fat, and low-sugar dairy (yogurt is ideal) can supply plenty of calcium. As far as vitamin D, well, vitamin D supplementation continues to be a topic of lively and livid debate among everyone, including competing guideline-authoring endocrine experts (see my Harvard Health Blog post on this). I hesitate to wander into that minefield again. But here goes…The scoop on vitamin D deficiencyThere is a large group of people who are likely to be deficient in vitamin D. It includes people with eating disorders; people who have had gastric bypass surgeries; those with malabsorption syndromes like celiac sprue; pregnant and lactating women; people who have dark skin; and those who wear total skin covering (and thus absorb less sunlight). In addition, people with or at risk for low bone density (perimenopausal and postmenopausal women, people diagnosed with other skeletal disorders, or who take certain medications), should discuss whether they need supplements and to have blood levels of vitamin D monitored.Many New England-dwelling (and Northern hemisphere) residents are at risk for a dip in vitamin D levels during the long, dark winter months. In my own practice I do consider that a risk factor, and I advise a vitamin D supplement of 1, 000 IUs daily. For people who would rather avoid a supplement but may need a boost of vitamin D, it is also found in some common foods, including sardines, salmon, tuna, cheese, egg yolks, and vitamin-fortified milk. I will add that, for those who fall into the “healthy community-dwelling adult” category, a supplement of anywhere from 400 to 2, 000 IUs of vitamin D daily is not likely to cause harm. Yes, vitamin D toxicity is a thing, usually seen at levels above 80 ng/ml, which causes excessive calcium to be released into the bloodstream. This is rare, but I have seen it in patients who took high-dose vitamin D supplementation of 50, 000 IUs weekly over a long period of time.Other important and effective ways to protect your bonesThere are other methods that may be more effective at maintaining bone health and reducing fracture risk. One that we can likely all agree on is regular physical activity. Weight-bearing exercise like walking, jogging, tennis, and aerobics definitely strengthens bones. Core exercises like yoga and Pilates can improve balance. All of this can help reduce falls and fracture risk.And so, in the end, I am recommending what I always end up recommending: a Mediterranean-style diet rich in colorful plants, plenty of legumes, fish, plus low-sugar, low-fat dairy and plenty of varied physical activity throughout your entire life… and maybe calcium and/or vitamin D supplementation for certain people, following a discussion with their doctors.Harvard medical school
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A tool that tracks and stops bacterial blight outbreaks in ricericetoday.irri.org/a-tool-that-tracks-and-stops-bacterial-blight-outbreaks-in-rice/A new, faster, and more accurate way of identifying infectious organisms—down to their genetic fingerprint—could finally put farmers a step ahead of bacterial blight. Severe bacterial blight infection in a susceptible rice variety from West Java, Indonesia. (Photo by R. Oliva)Severe bacterial blight infection in a susceptible rice variety from West Java, Indonesia. (Photo by R. Oliva)A revolutionary tool called the PathoTracer has been developed at the International Rice Research Institute (IRRI) and it can identify the exact strain of the bacterium that causes bacterial blight present in a field in a matter of days instead of several months of laboratory work.“It’s like a paternity test that uses DNA profiling, ” said Ricardo Oliva, a plant pathologist at IRRI. “It will not only tell you that you have bacterial blight in your plant. It will tell you the particular strain of the pathogen so that we can recommend varieties resistant to it.”For more than four years, Dr. Oliva and his team worked on deciphering the genetic code of Xanthomonas oryzae pv. oryzae, the pathogen that causes bacterial blight, to develop the test. Bacterial blight is one of the most serious diseases of rice. The earlier the disease occurs, the higher the yield loss—which could be as much as 70% in vulnerable varieties.“Bacterial blight is a persistent disease in rice fields, ” said Dr. Oliva. “The epidemic builds up every season when susceptible varieties are planted. The problem is that the bacterial strains vary from one place to another and farmers don’t know which are the resistant varieties for that region. We were always behind because the pathogens always moved and evolved faster.”Identifying the strains of bacterial blight present in the field requires a lot of labor and time. You need people to collect as many samples as they can over large areas to accurately monitor the pathogen population. In addition, isolating the pathogens in the lab is laborious and it typically takes several months or even a year to determine the prevalent strains in a region.The PathoTracer can identify the local bacteria in the field using small leaf discs as samples. The samples will be sent to a certified laboratory to perform the genetic test and the results will be analyzed by IRRI.The team that developed PathoTracer. Left row: Maritess Carillaga, Cipto Nugroho, Ian Lorenzo Quibod, and Genelou Grande. Right row: Veronica Roman-Reyna, Sapphire Thea Charlene Coronejo, and Dr. Oliva. Not in photo: Eula Gems Oreiro, EiEi Aung, and Marian Hanna Nguyen. (Photo by Isagani Serrano, IRRI)The team that developed PathoTracer. Left row (front to back): Maritess Carillaga, Cipto Nugroho, Ian Lorenzo Quibod, and Genelou Grande. Right row: Veronica Roman-Reyna, Sapphire Thea Charlene Coronejo, and Dr. Oliva. Not in photo: Eula Gems Oreiro, EiEi Aung, Epifania Garcia, Ismael Mamiit, and Marian Hanna Nguyen. (Photo by Isagani Serrano, IRRI)“It takes only a few days to analyze the samples, ” Dr. Oliva explained. “With the PathoTracer, we can bring a year’s work down to probably two weeks. Because the tool can rapidly and efficiently monitor the pathogen present in each season, the information can be available before the cropping season ends.”It’s like knowing the future, and predicting what would happen the next season can empower the farmers, according to Dr. Oliva.“Recognizing the specific local bacteria present in the current season can help us plan for the next, ” he added. “We can come up with a list of recommended rice varieties that are resistant to the prevalent pathogen strains in the locality. By planting the recommended varieties, farmers can reduce the risk of an epidemic in the next season and increase their profits.”The PathoTracer was pilot tested in Mindanao in the southern part of the Philippines in April 2017. The rains came early in the region, just after the peak of the dry season, and that triggered an outbreak of bacterial blight.“We went there and took samples from different fields, ” Dr. Oliva said. “By the end of April, we had the results and we were able to come up with a list of resistant varieties that could stop the pathogen. We submitted our recommendation to give farmers a choice in reducing the risk. If the farmers planted the same rice varieties in the succeeding rainy seasons, I am 100% sure the results would be very bad.”The PathoTracer can run thousands of samples and can, therefore, easily cover large areas, making it an essential tool for extension workers of agriculture departments and private-sector rice producers, or it can be incorporated into monitoring platforms such as the Philippine Rice Information System (PRiSM) or Pest and Disease Risk Identification and Management (PRIME) to support national or regional crop health decision-making.“National breeding programs could also make more informed decisions, ” Dr. Oliva said. “If you know the pathogen population in the entire Philippines, for example, the country’s breeding program could target those strains.”IRRI is interested in expanding the genetic testing tool to include rice blast and, further down the road, all bacteria, viruses, and fungi that infect rice.The speed at which PathoTracer can identify the strains of bacterial blight present in the field can be used for recommending resistant rice varieties to farmers for planting in the next cropping season. (Photo: IRRI)The speed at which PathoTracer can identify the strains of bacterial blight present in the field can be used for recommending resistant rice varieties to farmers for planting in the next cropping season. (Photo: IRRI)The PathoTracer has been tested in other Asian countries and IRRI expects to roll it out early in 2018. When it becomes available, the expected potential impact of the PathoTracer on a devastating disease that affects rice fields worldwide would be huge.“Imagine if this tool prevented bacterial blight outbreaks every season across Asia, ” said Dr. Oliva. “It’s super cool!”For more information about bacterial blight, see Section II, Chapter 2 of IRRI’s Rice Diseases Online Resource
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Clog Resistance of non-Pressure Based Flow CytometersBy Greg Kaduchak, PhD10.25.2017Flow cell clogs have been a long standing issue in flow cytometry. The small dimensions of the flow cell and fluidic path are susceptible to clogs especially when using larger or ‘sticky’ cells. In addition, historically, flow cytometer systems have been pressure-based which compounds this issue even more.In pressure-based systems, the particles are transported through the system by applying pressure to the fluid. It is a straightforward method to move the fluids through the small channels. To ensure a smooth delivery of fluids and particles through the flow cell without fluctuations, the systems employ pressure regulators. For those that have used these systems, it is a proven design to deliver particles in a flow cytometer and has been successful over the years. But, in the event of a clog, there is not much these systems can do.Figure 1(a) and (b) show what happens when a clog is encountered in a pressure-based fluidic system. When the system is in normal operation (a), the fluid is pushed through the system a specified pressure. For this example, we have used 7 psi. But, as seen in (b), when a clog is encountered the regulator keeps the system at 7 psi. No additional pressure is exerted to move the clog through the flow cell and the flow stops.Figure 1In contrast, in systems that employ positive displacement to drive the fluidic system (e.g. syringe pumps), the pressure is not held constant. These systems operate by a principle of constant volumetric flow. They are designed for fluid to flow with a specified volume delivery rate regardless of the pressure. An example of such a system facing a potential clog is shown in Figs. 1(c) and (d). As seen, the system operates at the same pressure as the pressure-based system when all is fine. But, once a clog is encountered, the system will build pressure to maintain the volumetric delivery rate. Pressure will build until the clog is displaced.The fluidic system in the Attune NxT Acoustic Focusing Flow Cytometers is based on positive displacement fluid delivery. For the purpose of robust clog removal, the system is outfit with a sensor that monitors the system pressure. When a potential clog is encountered, the pressure is allowed to build all the way up to 60 psi before safely shutting down the system. An additional benefit is used by the Attune NxT Flow Cytometer to keep the flow cell clean: a rinse cycle automatically runs between samples, this clears the sample in the flow cell with excess sheath fluid to prevent any cellular buildup.This feature has made the Attune flow cytometer platforms extremely clog resistant. Its install base has grown considerably since its initial launch more than two years ago, but still only a few clogs have been encountered by users of properly maintained instruments. Due to this resistance to clog, positive displacement systems are great from applications where cells are large and sticky, especially for tissue-based samples.
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In the future we won’t edit genomes—we’ll just print out new onesWhy redesigning the humble yeast could kick off the next industrial revolution.by Bryan Walsh February 16, 2018At least since thirsty Sumerians began brewing beer thousands of years ago, Homo sapiens has had a tight relationship with Saccharomyces cerevisiae, the unicellular fungus better known as brewer’s yeast. Through fermentation, humans were able to harness a microscopic species for our own ends. These days yeast cells produce ethanol and insulin and are the workhorse of science labs.That doesn’t mean S. cerevisiae can’t be further improved—at least not if Jef Boeke has his way. The director of the Institute for Systems Genetics at New York University’s Langone Health, Boeke is leading an international team of hundreds dedicated to synthesizing the 12.5 million genetic letters that make up a yeast’s cells genome.In practice, that means gradually replacing each yeast chromosome—there are 16 of them—with DNA fabricated on stove-size chemical synthesizers. As they go, Boeke and collaborators at nearly a dozen institutions are streamlining the yeast genome and putting in back doors to let researchers shuffle its genes at will. In the end, the synthetic yeast—called Sc2.0—will be fully customizable.“Over the next 10 years synthetic biology is going to be producing all kinds of compounds and materials with microorganisms, ” says Boeke. “We hope that our yeast is going to play a big role in that.”Think of the project as something like Henry Ford’s first automobile—hand built and, for now, one of a kind. One day, though, we may routinely design genomes on computer screens. Instead of engineering or even editing the DNA of an organism, it could become easier to just print out a fresh copy. Imagine designer algae that make fuel; disease-proof organs; even extinct species resurrected.Jef Boeke leads an effort to create yeast with a man-made genome.“I think this could be bigger than the space revolution or the computer revolution, ” says George Church, a genome scientist at Harvard Medical School.Researchers have previously synthesized the genetic instructions that operate viruses and bacteria. But yeast cells are eukaryotic—meaning they confine their genomes in a nucleus and bundle them in chromosomes, just as humans do. Their genomes are also much bigger.That’s a problem because synthesizing DNA is still nowhere near as cheap as reading it. A human genome can now be sequenced for $1, 000, with the cost still falling. By comparison, to replace every DNA letter in yeast, Boeke will have to buy $1.25 million worth of it. Add labor and computer power, and the total cost of the project, already under way for a decade, is considerably more.Along with Church, among others, Boeke is a leader of GP-write, an organization advocating for international research to reduce the cost of designing, engineering, and testing genomes by a factor of a thousand over the next decade. “We have all kinds of challenges facing ourselves as a species on this planet, and biology could have a huge impact on them, ” he says. “But only if we can drive down costs.”Bottom upA scientist named Ronald Davis at Stanford first suggested the possibility of synthesizing the yeast genome at a conference in 2004—though initially, Boeke didn’t see the point. “Why would anyone want to do this?” he recalls thinking.But Boeke came around to the idea that manufacturing a yeast genome might be the best way to comprehend the organism. By replacing each part, you might learn which genes are necessary and which the organism can live without. Some team members call the idea “build to understand.”“It’s a different take on trying to understand how living things work, ” says Leslie Mitchell, a postdoctoral fellow in the NYU lab and one of the main designers of the synthetic yeast. “We learn what gaps in our knowledge exist in a bottom-up genetic approach.”Joel Bader, a computer scientist at Johns Hopkins, signed on to develop software that let scientists see the yeast chromosomes on a screen and keep track of versions as they changed, like a Google Docs for biology. And in 2008, to make the DNA, Boeke launched an undergraduate course at Hopkins called “Build a Genome.” Students would learn basic molecular biology as each one assembled a continuous stretch of 10, 000 DNA letters that would go toward the synthetic-yeast project. Later, several institutions in China joined to share the workload, along with collaborators in Britain, Australia, and Japan.“We assign chromosomes to individual teams, like assigning a chapter of a book, and they have the freedom to decide how to do it, as long as it’s based 100 percent on what we design, ” says Patrick Cai, a synthetic biologist at the University of Manchester and the yeast project’s international coordinator.Next stepsIt took Boeke and his team eight years before they were able to publish their first fully artificial yeast chromosome. The project has since accelerated. Last March, the next five synthetic yeast chromosomes were described in a suite of papers in Science, and Boeke says that all 16 chromosomes are now at least 80 percent done. These efforts represent the largest amount of genetic material ever synthesized and then joined together.It helps that the yeast genome has proved remarkably resilient to the team’s visions and revisions. “Probably the biggest headline here is that you can torture the genome in a multitude of different ways, and the yeast just laughs, ” says Boeke.
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Sequencing Human Genome with Pocket-Sized “Nanopore” DeviceDr. Francis CollinsMinION sequencing deviceIt’s hard to believe, but it’s been almost 15 years since we successfully completed the Human Genome Project, ahead of schedule and under budget. I was proud to stand with my international colleagues in a celebration at the Library of Congress on April 14, 2003 (which happens to be my birthday), to announce that we had stitched together the very first reference sequence of the human genome at a total cost of about $400 million. As remarkable as that achievement was, it was just the beginning of our ongoing effort to understand the human genome, and to use that understanding to improve human health.That first reference human genome was sequenced using automated machines that were the size of small phone booths. Since then, breathtaking progress has been made in developing innovative technologies that have made DNA sequencing far easier, faster, and more affordable. Now, a report in Nature Biotechnology highlights the latest advance: the sequencing and assembly of a human genome using a pocket-sized device [1]. It was generated using several “nanopore” devices that can be purchased online with a “starter kit” for just $1, 000. In fact, this new genome sequence—completed in a matter of weeks—includes some notoriously hard-to-sequence stretches of DNA, filling several key gaps in our original reference genome.For most sequencing methods, DNA must be broken into smaller, more manageable fragments. That means all of the nucleotide “letters”— the As, Cs, Gs, and Ts—in the DNA code must be pieced back together in their correct order like a complex puzzle. While many methods are incredibly accurate at reassembling many parts of the puzzle, it’s much trickier to do this in highly repetitive stretches of DNA. When broken up, they produce puzzle pieces that are essentially identical.To get around that problem, some newer sequencing technologies are able to read out much longer stretches of DNA. In this latest report, an international team including Nicholas Loman at the University of Birmingham in the United Kingdom (U.K.), Matthew Loose at the University of Nottingham, U.K., and Adam Phillippy at NIH’s National Human Genome Research Institute, Bethesda, MD, relied on one such device: the hand-held MinION nanopore sequencer, produced by Oxford Nanopore Technologies.In fact, nanopore sequencing was named one of Science magazine’s “Breakthroughs of the Year” in 2016. The method involves threading single DNA strands through many tiny protein pores, i.e., nanopores, set in an electrically resistant polymer membrane. Inside the device, an ionic current is passed through the nanopore. When a single-stranded DNA molecule passes through the charged nanopore, it alters the current. In fact, the current is altered in different ways depending on which of DNA’s four unique nucletoides—adenine (A), cytosine (C), guanine (G), or thymine (T)—is passing through the pore. As a result, it’s possible to “read” off the DNA sequence, letter by letter!The nanopore sequencer was initially used primarily for sequencing smaller microbial genomes. In fact, Loman was part of a team that used the portable nanopore device to track Ebola and Zika viruses during the recent outbreaks in Africa and Brazil [2, 3]. The nanopore sequencer was also used on the International Space Station to do the very first DNA sequencing in zero gravity [4].The larger, more complex human genome represents a much stiffer challenge. But Loman and colleagues took on the challenge, betting that MinION was now up to the task based on recent improvements in its sequencing speed, computer software, and sample prep.The team, which included five labs in three countries, sequenced the complete genome of a well-studied human cell line in a matter of weeks. The researchers generated 91.2 gigabytes of DNA data, enough to cover the genome 30 times over, which helps to put the pieces together accurately. Most notably, they also generated ultra-long “reads” up to 882, 000 bases of contiguous DNA sequence. The researchers report that they have since read individual DNA molecules over a million bases long! Though the final cost ran about $23, 000 to sequence one human genome, further refinements should continue to drop the price.The real trick to getting such long reads is to prepare the DNA in such a way that the molecules don’t get cut or otherwise broken into small fragments, which the team has learned to do well. In fact, the team reports that in principle there may be no limit to the read-lengths that are possible using nanopore-based sequencing, including possibly entire chromosomes. The challenge will be getting the DNA molecules into the sequencing device without damaging them. Once a DNA molecule is threaded into a pore, there’s really no reason for it to stop until its passed all the way through.Despite those longer, easier-to-assemble reads, the researchers still required some big computers, including the high-performance computational resources in NIH’s Biowulf system, to make sense of the data, correct for errors, and piece together portions of the genome that had been impossible to assemble previously. For example, they resolved several highly repetitive genomic regions, including the sequences of some essential genes in immunity. They were also able to accurately estimate the lengths of highly repetitive telomeres, which act like “caps” at the tips of chromosomes. Telomere lengths are of great research interest for their implications in aging and cancer.Just as capabilities once only available through huge supercomputers can today be accessed though apps on smartphones, DNA sequencers continue to get better, smaller, and more portable. And as this study demonstrates, there’s no doubt that we’re pushing ever closer to a time when it may become both feasible and practical to sequence individual human genomes to bring greater precision to the delivery of health care for everyone.References:[1] Nanopore sequencing and assembly of a human genome with ultra-long reads. Jain M, Koren S, Miga KH, Quick J, Rand AC, Sasani TA, Tyson JR, Beggs AD, Dilthey AT, Fiddes IT, Malla S, Marriott H, Nieto T, O’Grady J, Olsen HE, Pedersen BS, Rhie A, Richardson H, Quinlan AR, Snutch TP, Tee L, Paten B, Phillippy AM, Simpson JT, Loman NJ, Loose M. Nature Biotech. 2018 Jan. 29. [Epub ahead of print][2] Real-time, portable genome sequencing for Ebola surveillance. Quick J, Loman NJ, Duraffour S, Simpson JT, Severi E, Cowley L, et al..Nature. 2016 Feb 11;530(7589):228-232.[3] Establishment and cryptic transmission of Zika virus in Brazil and the Americas. Faria NR, Quick J, Claro IM, Thézé J, de Jesus JG, et al. Nature. 2017 Jun 15;546(7658):406-410.[4] Nanopore DNA Sequencing and Genome Assembly on the International Space Station. Castro-Wallace SL, Chiu CY, John KK, Stahl SE, Rubins KH, McIntyre ABR, Dworkin JP, Lupisella ML, Smith DJ, Botkin DJ, Stephenson TA, Juul S, Turner DJ, Izquierdo F, Federman S, Stryke D, Somasekar S, Alexander N, Yu G, Mason CE7, Burton AS. Sci Rep. 2017 Dec 21;7(1):18022.Links:DNA Sequencing (National Human Genome Research Institute/NIH)Loman Lab (University of Birmingham, United Kingdom)Matt Loose (University of Nottingham, U.K.)Adam Phillippy (National Human Genome Research Institute/NIH)MinION (Oxford Nanopore Technologies, U.K.)NIH Support: National Human Genome Research Institute; National Cancer Institute
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A Resurgence in Natural Product-Based Drug DiscoveryAdvances in analytical technology are making the screening of natural products and their substructures more viable.Jan 24, 2018By Simon PearcePharmaceutical Technology's In the Lab eNewsletterVolume 13, Issue 2Natural products and their substructures have long been valuable starting points for medicinal chemistry and drug discovery. Since the earliest days of medicine, we’ve turned to nature for our treatments. From the application of digitalis extract as a remedy for heart failure, to the use of Vitamin C to prevent scurvy, many of the first drug treatments were developed by studying the medicinal effects of plants, and isolating the specific compounds responsible for their therapeutic properties. As the knowledge of medicinal chemistry and chemical synthesis advances, the pharmaceutical industry has become more adept at creating synthetic analogues of natural products to reduce the reliance on natural sources, or to improve drug properties such as therapeutic potency, bioavailability, or metabolism by carefully modifying a molecule’s structure (1). Indeed, it’s thought that approximately 40% of drugs available on the market today are derived from chemical structures found in nature (2, 3). Yet over the past few decades, the influence of natural products on drug discovery has notably reduced, in part due to the perceived difficulties of isolating and synthesizing these complex molecules, as well as the challenges associated with screening them using high throughput assays, which are commonly used to identify potential lead compounds.The industry, however, could be at a turning point. In recent years, there has been a resurgence of interest in the inclusion of natural products and their substructures in compound screening collections. Here, the author considers how advances in technology and adoption of alternative screening strategies are playing a role in revitalizing natural product-based drug discovery.While nature has been an important source of medicines throughout human history, the value of natural products in drug discovery has been somewhat overlooked in recent times. There is, however, a resurgence of interest in their use, driven to a large extent by the recognition of their enormous potential in the search for new antimicrobials and their efficacy to challenging targets based on the disruption of protein–protein interactions. Alternative screening strategies, such as fragment-based and phenotypic approaches, as well as advances in assay detection technology, have the potential to open up unexplored areas of chemical space populated by these important structures in the search for new and effective treatments.
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Harvard Medical SchoolControlling your weight is key to lowering stroke riskThere is a lot you can do to lower your chances of having a stroke. Even if you've already had a stroke or TIA ("mini-stroke"), you can take steps to prevent another.Controlling your weight is an important way to lower stroke risk. Excess pounds strain the entire circulatory system and can lead to other health conditions, including high blood pressure, diabetes, high cholesterol, and obstructive sleep apnea. But losing as little as 5% to 10% of your starting weight can lower your blood pressure and other stroke risk factors.Protect your brain: That’s the strategy that Harvard doctors recommend in this report on preventing and treating stroke. Whether you’ve already had a mini-stroke or a major stroke, or have been warned that your high blood pressure might cause a future stroke, Stroke: Diagnosing, treating, and recovering from a "brain attack" provides help and advice.Of course, you'll need to keep the weight off for good, not just while you're on a diet. The tips below can help you shed pounds and keep them off:Move more. Exercise is one obvious way to burn off calories. But another approach is to increase your everyday activity wherever you can — walking, fidgeting, pacing while on the phone, taking stairs instead of the elevator.Skip the sipped calories. Sodas, lattes, sports drinks, energy drinks, and even fruit juices are packed with unnecessary calories. Worse, your body doesn't account for them the way it registers solid calories, so you can keep chugging them before your internal "fullness" mechanism tells you to stop. Instead, try unsweetened coffee or tea, or flavor your own sparkling water with a slice of lemon or lime, a sprig of fresh mint, or a few raspberries.Eat more whole foods. If you eat more unprocessed foods — such as fruits, vegetables, and whole grains — you'll fill yourself up on meals that take a long time to digest. Plus, whole foods are full of vitamins, minerals, and fiber and tend to be lower in salt — which is better for your blood pressure, too.Find healthier snacks. Snack time is many people's downfall — but you don't have to skip it as long as you snack wisely. Try carrot sticks as a sweet, crunchy alternative to crackers or potato chips, or air-popped popcorn (provided you skip the butter and salt and season it with your favorite spices instead). For a satisfying blend of carbs and protein, try a dollop of sunflower seed butter on apple slices.For more information on lifestyle changes you can make to help prevent a stroke, buy Stroke: Diagnosing, treating, and recovering from a "brain attack, " a Special Health Report from Harvard Medical School.Stroke: Know when to act, and act quicklyIdentifying and treating a stroke as quickly as possible can save brain cells, function, and lives. Everyone should know the warning signs of a stroke and when to get help fast.The warning signs of a stroke can begin anywhere from a few minutes to days before a stroke actually occurs. The National Stroke Association has devised the FAST checklist to help determine whether a person is having a stroke.Act FASTIf the answer to any of the questions below is yes, there's a high probability that the person is having a stroke.Face: Ask the person to smile. Does one side of the face droop?Arms: Ask the person to raise both arms. Does one arm drift downward?Speech: Ask the person to repeat a simple sentence. Are the words slurred? Does he or she fail to repeat the sentence correctly?Time: If the answer to any of these questions is yes, time is important! Call the doctor or get to the hospital fast. Brain cells are dying.When stroke symptoms occur, quick action is vital. If you think you or someone with you is having a stroke, call the doctor. Ideally, the person affected should be taken to a hospital emergency room that has expertise and experience in treating stroke as it occurs (called acute stroke). If you or someone you love is at high risk for having a stroke, you should know the name and location of the nearest hospital that specializes in treating acute stroke.The goal of stroke treatment is to restore blood circulation before brain tissue dies. To prevent brain cell death that is significant enough to cause disability, treatment is most effective if it starts within 60 minutes of the onset of symptoms. But it can still be very effective if given within 3 hours of symptom onset.An important goal of ongoing stroke research is to find treatments that can buy time by protecting the person's brain until blood circulation is restored, which can increase the chances of survival and decrease the chances of disability.
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