Archive for the ‘Biotechnology’ Category
Scientists have used the cloning technique that led to Dolly the sheep to turn human skin into embryonic stem cells – which can make any tissue in the body.
The US team overcame technical problems that had frustrated researchers for more than a decade to create batches of the bodys master cells from donated skin.
The work will spark fresh interest in the use of cloning in medical research, and reignite the controversy over a procedure that demands a supply of human eggs, and the creation and destruction of early stage embryos. The US group employed the technique to make embryonic stem cells that were genetically matched to individuals. Such cells could be used to study diseases in exquisite detail, and regenerate damaged organs and tissues.
A human egg before nuclear extraction and fusion with a skin cell. The resulting embryonic stem cells were genetically identical to the skin donor. Photograph: Oregon Health & Science University
They’re man’s best friend, and they may be one of the heart’s best allies as well.A panel of heart disease experts convened by the American Heart Association AHA reviewed research linking heart health and owning a pet and found that owning a pet is “probably associated” with a lower risk of heart disease for those without a history of heart problems, and with greater survival rates among heart disease patients.
In a New York laboratory, a special group of mice is destined to outlive their cage-mates. Their muscles will stay strong for longer. Their brains will stay sharp for longer. When they eventually die, they will have seen more months than their peers.The secret to their longevity isn’t a drug or a special diet. Instead, Dongsheng Cai from the Albert Einstein College of Medicine simply reduced the levels of a single protein called NF-kB in part of the brain called the hypothalamus. That was enough to extend their lives.
When a group of genetically identical mice lived in the same complex enclosure for 3 months, individuals that explored the environment more broadly grew more new neurons than less adventurous mice, according to a study published today (May 9) in Science. This link between exploratory behavior and adult neurogenesis shows that brain plasticity can be shaped by experience and suggests that the process may promote individuality, even among genetically identical organisms.
“This is a clear and quantitative demonstration that individual differences in behavior can be reflected in individual differences in brain plasticity,” said Fred Gage of the Salk Institute for Biological Studies in La Jolla, California, who was not involved the study. “I don’t know of another clear example of that . . . and it tells me that there is a tighter relationship between [individual] experiences and neurogenesis than we had previously thought.”
Posted May 9, 2013on:
Doctors announced today that two-and-a-half year old Hannah Warren just became the youngest person in history to receive a bioengineered organ transplant, a new windpipe made of a synthetic scaffold and her own stem cells. The nine-hour long procedure was performed April 9th, at Children’s Hospital of Illinois in Peoria, but the results were just made public. Doctors expect that Warren will be able to return home in a few months and breathe, eat, drink and swallow using the new windpipe, all of which she couldn’t do without the aid of machines until now.
Furthermore, because the procedure was performed using her own cells and no donor organ, there is next to zero risk of rejection.
Mutations on a single gene appear to increase the risk for both an unusual sleep disorder and migraines, a team reports in Science Translational Medicine.
The finding could help explain the links between sleep problems and migraines. It also should make it easier to find new drugs to treat migraines, researchers say.
Scientists have made a breakthrough that could save patient’s lives and open up the possibilities for underwater exploration.
A team at Boston Children’s Hospital have invented a micro-particle that can be injected into your bloodstream to oxygenate your blood – without any help being required from your lungs.
The particles are able to keep a patient alive for up to 30 minutes after respiratory failure – which is normally enough time to prevent a heart attack or brain damage due to oxygen deprivation.
In a promising development for diabetes treatment, researchers have developed a network of nanoscale particles that can be injected into the body and release insulin when blood-sugar levels rise, maintaining normal blood sugar levels for more than a week in animal-based laboratory tests. The work was done by researchers at North Carolina State University, the University of North Carolina at Chapel Hill, the Massachusetts Institute of Technology and Children’s Hospital Boston. Read the rest of this entry »
Computer simulations show that high blood pressure can be entirely explained by arterial stiffening as we age, say researchers.
High blood pressure dramatically increases the risk of a stroke or heart attack and so is one of the biggest silent killers in the Western world.
But while there are several known mechanisms that cause high blood pressure, some 90% of cases are entirely unexplained. Physicians believe that various factors increase the risk of high blood pressure, such as age, family history, lack of exercise and so on. But the actual mechanism that causes the increase is hotly debated.
Flu during pregnancy may increase the risk of the unborn child developing bipolar disorder later in life, research suggests.
A study of 814 expectant women, published in JAMA Psychiatry, showed that infection made bipolar four times more likely. The overall risk remained low, but it echoes similar findings linking flu and schizophrenia.
Experts said the risks were small and women should not worry.
The mysterious coronavirus that emerged in the Middle East last year may have started spreading from person to person. Health authorities in Saudi Arabia revealed this week that a cluster of cases in the east of the country were all linked to a single hospital. The similarity of the outbreak to the SARS epidemic of a decade ago is sending a shudder through public health experts worldwide.
Ziad Memish, the Saudi deputy health minister, told ProMed, the online forum on emerging disease, that 13 people in the kingdom fell ill with the virus – now called MERS – in the second half of April. Their average age was over 50, they had other problems such as heart or kidney disease or diabetes – and they had all visited the Al-Moosa Hospital in the town of Hofuf, shortly before developing a high fever and breathing problems
key type of human brain cell developed in the laboratory grows seamlessly when transplanted into the brains of mice, UC San Francisco researchers have discovered, raising hope that these cells might one day be used to treat people with Parkinson’s disease, epilepsy, and possibly even Alzheimer’s disease, as well as and complications of spinal cord injury such as chronic pain and spasticity.
“We think this one type of cell may be useful in treating several types of neurodevelopmental and neurodegenerative disorders in a targeted way,” said Arnold Kriegstein, MD, PhD, director of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at UCSF and co-lead author on the paper.
The researchers generated and transplanted a type of human nerve-cell progenitor called the medial ganglionic eminence (MGE) cell, in experiments described in the May 2 edition of Cell Stem Cell. Development of these human MGE cells within the mouse brain mimics what occurs in human development, they said. Read the rest of this entry »
The 1918 Spanish flu killed up to 40 million people. The swine flu pandemic in 2009 killed an estimated 284,000. Now, scientists have discovered a substance that could help doctors save lives during future influenza pandemics. Eritoran, a compound under investigation as a sepsis drug, dramatically reduces deaths from influenza in mice.
At the moment, doctors have only one class of compounds available to combat influenza. The drugs, Tamiflu and Relenza, block neuraminidase, a surface protein that influenza viruses need to leave the cell after reproduction. The drugs, taken orally, have to be given soon after infection to be effective, however, and some flu strains have developed resistance against them. A few scientists have also questioned the safety and efficacy of the compounds, which many countries stockpiled during the 2009 H1N1 pandemic.
Instead of targeting the virus, immunologist Stefanie Vogel at the University of Maryland, Baltimore, tried to interfere with the host immune system.
Heather Sellers has prosopagnosia, more commonly known as face blindness. “I can’t remember any image of the human face. It’s simply not special to me,” she says. “I don’t process them like I do a car or a dog. It’s not a visual problem, it’s a perception problem.”
The condition is estimated to affect around 2.5 per cent of the population, and it’s common for those who have it not to realise that anything is wrong. “In many ways it’s a subtle disorder,” says Heather. “It’s easy for your brain to compensate because there are so many other things you can use to identify a person: hair colour, gait or certain clothes. But meet that person out of context and it’s socially devastating.”
Drew Endy wants to build a programming language for the body.
Endy is the co-director of the International Open Facility Advancing Biotechnology — BIOFAB, for short — where he’s part of a team that’s developing a language that will use genetic data to actually program biological cells. That may seem like the stuff of science fiction, but the project is already underway, and the team intends to open source the language, so that other scientists can use it and modify it and perfect it.
The effort is part of a sweeping movement to grab hold of our genetic data and directly improve the way our bodies behave — a process known as bioengineering. With the Supreme Court exploring whether genes can be patented, the bioengineering world is at crossroads, but scientists like Endy continue to push this technology forward.
Posted April 13, 2013on:
Like finally seeing all the gears of a watch and how they work together, researchers from UCLA and UC Berkeley have, for the first time ever, solved the puzzle of how the various components of an entire telomerase enzyme complex fit together and function in a three-dimensional structure.
The three-dimensional electron microscopy structure of the complete Tetrahymena telomerase enzyme complex, with previously solved high-resolution structures modeled in. (Credit: Jiansen Jiang, Edward Miracco/UCLA Chemistry and Biochemistry)
Scientists have found a way to “read” dreams, a study suggests.
Researchers in Japan used MRI scans to reveal the images that people were seeing as they entered into an early stage of sleep.
Writing in the journal Science, they reported that they could do this with 60% accuracy.
The team now wants to see if brain activity can be used to decipher other aspects of dreaming, such as the emotions experienced during sleep.
In 2002 the Center for Disease Control estimated that autism affected about 1 in 150 children. By 2012 the CDC estimate had increased to 1 in 88. Now, according to the latest revision of the estimate recently released, autism affects 1 in 50 children. That’s a phenomenal 300 percent increase in 11 years. But do the numbers reflect a real increase in the incidence of autism or are previously undiagnosed cases now being diagnosed? The authors of the study tend to think it’s the latter, but others question whether the increase can be explained entirely by wider diagnoses.
In recent decades there has been a consistent increase in the reported prevalence of autism. Two National Health Interview Surveys, national telephone surveys conducted by the CDC, showed prevalence to increase almost four-fold between a 1997 – 1999 survey and a 2006 – 2008 survey. Concurrently, the CDC’s Autism and Developmental Disabilities Monitoring Network showed a 78 percent increase in autism spectrum disorder (ASD), that includes all variants of disease related to autism, between 2002 and 2008.
The visible brain has arrived — the consistency of Jell-O, as transparent and colorful as a child’s model, but vastly more useful.
Scientists at Stanford University reported on Wednesday that they have made a whole mouse brain, and part of a human brain, transparent, so that networks of neurons that receive and send information can be highlighted in stunning color and viewed in all their three-dimensional complexity without slicing up the organ.
Credit: Deisseroth Lab
A three-dimensional rendering of a “clarified” brain, as seen from below.
Scientists have decoded the genome of the western painted turtle, one of the most abundant turtles on Earth, finding clues to their longevity and ability to survive without oxygen during long winters spent hibernating in ice-covered ponds.
Understanding the natural mechanisms turtles use to protect the heart and brain from oxygen deprivation may one day improve treatments for heart attacks or strokes, the researchers say. Both can lead to severe disability or death within minutes in patients deprived of oxygen.
Dr. Stanley Hazen of the Cleveland Clinic, who led the study, and his colleagues had accumulated evidence for a surprising new explanation of why red meat may contribute to heart disease. And they were testing it with this early morning experiment.
The researchers had come to believe that what damaged hearts was not just the thick edge of fat on steaks, or the delectable marbling of their tender interiors. In fact, these scientists suspected that saturated fat and cholesterol made only a minor contribution to the increased amount of heart disease seen in red-meat eaters. The real culprit, they proposed, was a little-studied chemical that is burped out by bacteria in the stomach after people eat red meat. It is quickly converted by the liver into yet another little-studied chemical called TMAO that gets into the blood and increases the risk of heart disease.
The Rally for Medical Research will unite millions of Americans across the country to call on our nations policymakers to make life-saving medical research funding a national priority. This unified call to action will raise awareness about the critical need for a sustained investment in the National Institutes of Health to improve health, spur more progress, inspire more hope and save more lives.
Weight loss after gastric band surgery may be partly caused by changes to micro-organisms that live in the gut, say US researchers.A study in mice has shown that surgery causes different types of bacteria to colonise the gut.Transferring samples of those bacteria into healthy mice caused them to rapidly lose weight without surgery.But the Harvard University researchers said they could not yet explain the mechanism behind their results.There are differences in the bacteria in the stomachs and intestines of obese people compared with those who are of a normal weight.
And you thought it was all about the neurons.
In an experiment that might seem like something only a mad scientist would conjure, researchers injected human brain cells into the brains of mice to see how it would affect the way the mice thought. It did: the mice got smarter. But the cognition boosting cells weren’t neurons, they were the red-headed step-children of neuroscience called astrocytes. The study turns on its head the role historically attributed to astrocytes of simply supporting the all important function of neurons without playing a significant role in how we learn and think. It may very well be that humans owe much of their unique cognitive capabilities to astrocytes.
If biologists could put computational controls inside living cells, they could program them to sense and report on the presence of cancer, create drugs on site as they’re needed, or dynamically adjust their activities in fermentation tanks used to make drugs and other chemicals. Now researchers at Stanford University have developed a way to make genetic parts that can perform the logic calculations that might someday control such activities.
The Stanford researchers’ genetic logic gate can be used to perform the full complement of digital logic tasks, and it can store information, too. It works by making changes to the cell’s genome, creating a kind of transcript of the cell’s activities that can be read out later with a DNA sequencer. The researchers call their invention a “transcriptor” for its resemblance to the transistor in electronics. “We want to make tools to put computers inside any living cell—a little bit of data storage, a way to communicate, and logic,” says Drew Endy, the bioengineering professor at Stanford who led the work.
Social isolation is associated with a higher risk of death in older people regardless of whether they consider themselves lonely, research suggests.A study of 6,500 UK men and women aged over 52 found that being isolated from family and friends was linked with a 26% higher death risk over seven years.Whether or not participants felt lonely did not alter the impact of social isolation on health.
Scientists scanning the human brain can now tell whom a person is thinking of, the first time researchers have been able to identify what people are imagining from imaging technologies.
Work to visualize thought is starting to pile up successes. Recently, scientists have used brain scans to decode imagery directly from the brain, such as what number people have just seen and what memory a person is recalling. They can now even reconstruct videos of what a person has watched based on their brain activity alone. Cornell University cognitive neuroscientist Nathan Spreng and his colleagues wanted to carry this research one step further by seeing if they could deduce the mental pictures of people that subjects conjure up in their heads.
High salt intake isn’t just a concern for those with high blood pressure or heart disease anymore.
Three new studies, published together in the journal Nature, are raising the alarm that eating too much salt may put you at risk for a host of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis.
A team of researchers from Scotland has used a novel 3D printing technique to arrange human embryonic stem cells (hESCs) for the very first time.
It is hoped that this breakthrough, which has been published today, 5 February, in the journal Biofabrication, will allow three-dimensional tissues and structures to be created using hESCs, which could, amongst other things, speed up and improve the process of drug testing.
Read the rest of this entry »
Men taking calcium supplements may be running a nearly 20 percent increased risk of dying from cardiovascular disease, a new study suggests.Both men and women take calcium supplements to prevent bone loss. In this study of calcium intake, the risk of dying from heart disease was higher for men but not for women.
Posted February 4, 2013on:
There’s a wobbly new biochemical structure in Burckhard Seelig’s lab at the University of Minnesota that may resemble what enzymes looked like billions of years ago, when life on earth began to evolve – long before they became ingredients for new and improved products, from detergents to foods and fuels.
Seelig created the fledgling enzyme by using directed evolution in the laboratory. Working with colleague Gianluigi Veglia, graduate student Fa-An Chao, and other team members, he subsequently determined its structure, which made its debut December 9 as an advance online publication in Nature Chemical Biology. Lab tests show that the enzyme (a type of RNA ligase, which connects two RNA molecules) functions like natural enzymes although its structure looks very different and it is flexible rather than rigid. Seelig speculates the new protein resembles primordial enzymes, before their current structures evolved.
3-D structure of the evolved enzyme (an RNA ligase), using 10 overlaid snapshots. In the top region, the overlays show the range of bending and folding flexibility in the amino acid chain that forms the molecule. The two gray balls are zinc ions. (University of Minnesota) Read the rest of this entry »
Alya Red is a project of the Barcelona Supercomputing Center for simulating a human heart. In this video we explain the scientific background of the project, and show scientific visualizations of simulations using the computational electromechanical model applied to a rabbit heart.
To get a clear picture of what’s happening inside a cell, scientists need to know the locations of thousands of proteins and other molecules. MIT chemists have now developed a technique that can tag all of the proteins in a particular region of a cell, allowing them to more accurately map those proteins.
“That’s a holy grail for biology — to be able to get spatially and temporally resolved molecular maps of living cells,” says Alice Ting, the Ellen Swallow Richards Associate Professor of Chemistry at MIT. “We’re still really far from that goal, but the overarching motivation is to get closer to that goal.”
MIT chemists have devised a way to identify which proteins are present in different compartments of the mitochondria.
IMAGE: JEFF MARTELL, HYUN-WOO RHEE AND PENG ZOU
Dendritic cells trigger an adaptive immune response by activating two major classes of T lymphocytes—cytotoxic T cells that can kill infected host cells, and helper T cells that direct the activities of other immune cells. Cytotoxic T cells recognize class I MHC receptors loaded with antigen, whereas helper T cells recognize class II MHC-peptide. Dendritic cells constitutively express high levels of both class I and class II MCH molecules, making them the most potent activators of T cells, capable of stimulating even “naive” T cells that have never encountered antigen.
Image: A human lymphocyte (pink pseudocolor) scans the surface of a dendritic cell (blue pseudo-color). The image was obtained using a field emission scanning electron microscope. Scale bar 1µm.
Twenty year old Brooke Greenberg hasn’t grown since age five. For the last 15 years mystified doctors have been unable to explain the cause for Brooke’s disorder that has kept her aging in check. At age twenty, she maintains the physical and mental appearance of a toddler.
Eric Shadt wants to solve this most bizarre of medical mysteries. Director of the Icahn Institute for Genomics and Multiscale Biology at the Mount Sinai Medical Center in New York, Shadt is leading research to uncover the genetic cause for Brooke’s condition.
Because hormones control many of the maturation processes, one of the first things the research team looked at was to see if Brooke’s own hormone levels might be abnormal. In a piece he wrote on Katie Couric’s website on whose show he and the Greenberg family recently appeared, Shadt explained that Brooke “has no apparent abnormalities in her endocrine system, no gross chromosomal abnormalities, or any of the other disruptions known to occur in humans that can cause developmental issues.”
The researchers are now are painstakingly analyzing Brooke’s entire genome in search of unique mutations. Needless to say, it is a formidable undertaking. “Cracking the code on Brooke’s condition,” Shadt wrote, “is the proverbial searching for a needle in a haystack, since likely there is one or a small number of letters changed in Brooke’s genome that has caused her condition.”
We humans have long wondered how, exactly, we develop from embryos into adults. This photo of an embryonic smooth muscle cell hints at the tremendous complexity of this fundamental biological mystery. And for those of you who might be wondering just what smooth muscles are, they’re the involuntary muscles found in places like the walls of our blood vessels, the digestive tract, the bladder, and the respiratory system.
This exquisite photo was produced using laser scanning confocal microscopy — a precise imaging method that includes the dimension of depth for scientific analysis. Here, green is used to label thin filaments of the protein actin, which is a key component of the cell’s cytoskeleton, and blue indicates another protein, called vinculin, which is enriched in locations involved in cell-cell adhesion.
Credit: Vira V. Artym, National Institute of Dental and Craniofacial Research, NIH
Leprosy bacteria can reprogram cells to revert to a stem-cell-like state, able to mature into different cell types, researchers report today in Cell1.
The scientists stumbled on the discovery while researching the way leprosy spreads around the body. The mechanism of the hijacking is unclear, but reproducing it could lead to new stem-cell-based therapeutic strategies.
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Developed in 1897 by the German chemist Felix Hoffmann, aspirin, or acetylsalicylic acid, has long proved its value as an analgesic. Two millenniums before that, Hippocrates, the father of modern medicine, used its active ingredient — which he extracted from the bark and leaves of the willow tree — to help alleviate pain and fevers.
Since then, we’ve gained insight into both the biological mechanism and the effects of this chemical compound. Many high-quality research studies have confirmed that the use of aspirin substantially reduces the risk of cardiovascular disease. Indeed, the evidence for this is so abundant and clear that, in 2009, the United States Preventive Services Task Force strongly recommended that men ages 45 to 79, and women ages 55 to 79, take a low-dose aspirin pill daily, with the exception for those who are already at higher risk for gastrointestinal bleeding or who have certain other health issues. (As an anticoagulant, aspirin can increase the risk of bleeding — a serious and potentially deadly issue for some people.)
Drug Stimulates Regeneration of Sound-Sensing Hair Cells and Partial Recovery of Hearing in Deaf Mice
Posted January 16, 2013on:
Listen up, live music fans. The hearing loss caused by exposure to loud noise can be at least partially reversed with drugs, according to a study published by U.S. and Japanese researchers last week in the journal Neuron.
The work is the first proof that a drug can spur regeneration of the mammalian ear’s sound-detecting hair cells, which can be damaged by noise exposure. While the hair cells of some animals, such as birds, can regenerate on their own, the hair cells of humans and other mammals cannot. The cells may be damaged by infection or as a side effect of certain drugs as well as after exposure to loud noises.
Sound sensors: The delicate sound-detecting cells in the inner ear can be damaged and die after exposure to loud noises or toxic compounds (top), but they can be regenerated with a drug (bottom).
Repression of a single protein in ordinary fibroblasts is sufficient to directly convert the cells – abundantly found in connective tissues – into functional neurons. The findings, which could have far-reaching implications for the development of new treatments for neurodegenerative diseases like Huntington’s, Parkinson’s and Alzheimer’s, will be published online in advance of the January 17 issue of the journal Cell.
Physicians may soon have a new way to screen patients for Barrett’s esophagus, a precancerous condition usually caused by chronic exposure to stomach acid. Researchers at the Wellman Center for Photomedicine at Massachusetts General Hospital (MGH) have developed an imaging system enclosed in a capsule about the size of a multivitamin pill that creates detailed, microscopic images of the esophageal wall. The system has several advantages over traditional endoscopy.
“This system gives us a convenient way to screen for Barrett’s that doesn’t require patient sedation, a specialized setting and equipment, or a physician who has been trained in endoscopy,” says Gary Tearney, MD, PhD, of the Wellman Center and the MGH Pathology Department, corresponding author of the report receiving online publication in Nature Medicine. “By showing the three-dimensional, microscopic structure of the esophageal lining, it reveals much more detail than can be seen with even high-resolution endoscopy.”
Inch-long endomicroscopy capsule contains rotating infrared laser and sensors for recording reflected light. (Michalina Gora, PhD, and Kevin Gallagher, Wellman Center for Photomedicine, Massachusetts General Hospital)
Epileptic seizures occur when neurons in the brain become excessively active. However, a new study from MIT neuroscientists suggests that some seizures may originate in non-neuronal cells known as glia, which were long believed to play a mere supporting role in brain function.
In a study of fruit flies, the researchers identified a glial-cell mutation that makes the flies much more prone to epileptic seizures. Mutations in the gene, which influences glial cells’ communication with neurons, appear to make neurons much more excitable. That excitability makes the flies more likely to seize in response to environmental stimuli, such as extreme temperatures.
Finding ways to diagnose cancer earlier could greatly improve the chances of survival for many patients. One way to do this is to look for specific proteins secreted by cancer cells, which circulate in the bloodstream. However, the quantity of these biomarkers is so low that detecting them has proven difficult.
A new technology developed at MIT may help to make biomarker detection much easier. The researchers, led by Sangeeta Bhatia, have developed nanoparticles that can home to a tumor and interact with cancer proteins to produce thousands of biomarkers, which can then be easily detected in the patient’s urine.
These nanoparticles created by MIT engineers can act as synthetic biomarkers for disease. The particles (brown) are coated with peptides (blue) that are cleaved by enzymes (green) found at the disease site. The peptides then accumulate in the urine, where they can be detected using mass spectrometry.
Image: Justin H. Lo
A new study from researchers at MIT and Stanford University pinpoints brain cells that appear to be critically involved in depression, offering a possible target for new, more effective antidepressants.
By stimulating these cells to deliver dopamine to other parts of the brain, the researchers were able to immediately eliminate symptoms of depression in mice. They also induced depression in normal mice by shutting off the dopamine source.
The findings could help researchers develop antidepressants that are more precisely targeted, says Kay Tye, an assistant professor of brain and cognitive sciences at MIT and one of the lead authors of a paper on the work appearing in the Dec. 12 online edition of Nature.
The first genetically engineered GE animal for human consumption — a fast-growing salmon — has come a step closer to the dinner table, with a piece of paperwork posted online today by the US Food and Drug Administration FDA.The FDA’s draft environmental assessment concludes that the fish poses no foreseeable risk to nature. After 60 days of public comment, the FDA may issue a final assessment and approval — at which time AquaBounty, of Maynard, Massachusetts, can begin selling the fish.
Posted December 15, 2012on:
The health of most of the planet’s population is rapidly coming to resemble that of the United States, where death in childhood is rare, too much food is a bigger problem than too little, and life is long and often darkened by disability.
High blood pressure is now the leading “risk factor” for disease around the world. Alcohol use is third. Low-back pain now causes more disability than childbirth complications or anemia.