Are you smarter than a 5-year-old? Preschoolers can do algebra

Millions of high school and college algebra students are united in a shared agony over solving for x and y, and for those to whom the answers don’t come easily, it gets worse: Most preschoolers and kindergarteners can do some algebra before even entering a math class.In a just-published study in the journal Developmental Science, lead author and post-doctoral fellow Melissa Kibbe and Lisa Feigenson, associate professor of psychological and brain sciences at Johns Hopkins University’s Krieger School of Arts and Sciences, find that most preschoolers and kindergarteners, or children between 4 and 6, can do basic algebra naturally.”These very young children, some of whom are just learning to count, and few of whom have even gone to school yet, are doing basic algebra and with little effort,” Kibbe said. “They do it by using what we call their ‘Approximate Number System:’ their gut-level, inborn sense of quantity and number.”The “Approximate Number System,” or ANS, is also called “number sense,” and describes humans’ and animals’ ability to quickly size up the quantity of objects in their everyday environments. Humans and a host of other animals are born with this ability and it’s probably an evolutionary adaptation to help human and animal ancestors survive in the wild, scientists say.Previous research has revealed some interesting facts about number sense, including that adolescents with better math abilities also had superior number sense when they were preschoolers, and that number sense peaks at age 35.Kibbe, working in Feigenson’s lab, wondered whether preschool-age children could harness that intuitive mathematical ability to solve for a hidden variable, or in other words, to do something akin to basic algebra before they ever received formal classroom mathematics instruction. The answer was “yes,” at least when the algebra problem was acted out by two furry stuffed animals — Gator and Cheetah — using “magic cups” filled with objects like buttons, plastic doll shoes and pennies.In the study, children sat down individually with an examiner who introduced them to the two characters, each of whom had a cup filled with an unknown quantity of items. Children were told that each character’s cup would “magically” add more items to a pile of objects already sitting on a table. But children were not allowed to see the number of objects in either cup: they only saw the pile before it was added to, and after, so they had to infer approximately how many objects Gator’s cup and Cheetah’s cup contained.At the end, the examiner pretended that she had mixed up the cups, and asked the children — after showing them what was in one of the cups — to help her figure out whose cup it was. The majority of the children knew whose cup it was, a finding that revealed for the researchers that the pint-sized participants had been solving for a missing quantity, which is the essence of doing basic algebra.”What was in the cup was the x and y variable, and children nailed it,” said Feigenson, director of Johns Hopkins Laboratory for Child Development. “Gator’s cup was the x variable and Cheetah’s cup was the y variable. We found out that young children are very, very good at this. It appears that they are harnessing their gut level number sense to solve this task.”If this kind of basic algebraic reasoning is so simple and natural for 4, 5 and 6-year-olds, the question remains why it is so difficult for teens and others.”One possibility is that formal algebra relies on memorized rules and symbols that seem to trip many people up,” Feigenson said. …

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Agencies often hindered in addressing health concerns from industrial animal production

State regulatory agencies face barriers and often take limited action when confronted with public health concerns resulting from industrial food animal production operations. This is according to a new study led by researchers at the Johns Hopkins Center for a Livable Future who examined agency responses to community health concerns. They found that agencies with jurisdiction over industrial food animal production operations are unable to address concerns primarily due to narrow regulations, a lack of public health expertise, and limited resources. The results are featured today online in PLOS ONE.”Despite the well-established health risks associated with living and working near industrial food animal production operations, regulation of these sites is limited and characterized by a patchwork of different regulatory approaches from state to state,” said Jillian Fry, PhD, MPH, a project director at the Johns Hopkins Center for a Livable Future. “Common across most states, however, is delegating the permitting to an agency without a primary mandate to address public health, which raises concerns that public health issues may not be adequately monitored or addressed. Our study found that permitting and agriculture agencies’ response to health-based industrial farm animal production concerns are constrained by narrow regulations, a lack of public health expertise, and limited resources. In addition, most agency staff believed health departments should play a role in addressing citizen concerns related to industrial food animal production operations.”Researchers conducted semi-structured qualitative interviews with staff at 12 state agencies in seven states. The agencies were selected based on high volumes of industrial food animal production or a rapid increase in the number of industrial food animal production operations within their state. The interviews were conducted to gather information regarding agency involvement in regulating operations, the frequency and type of contacts received about public health concerns, how the agency responds to such contacts and barriers to additional involvement.Previous studies have shown air near animal production sites to contain hydrogen sulfide, particulate matter, and allergens. Exposure to these emissions has been associated with multiple respiratory, cardiovascular and neurological health problems. …

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Many stroke patients on ‘clot-busting’ tPA may not need long stays in ICU

A Johns Hopkins study of patients with ischemic stroke suggests that many of those who receive prompt hospital treatment with “clot-busting” tissue plasminogen activator (tPA) therapy can avoid lengthy, restrictive monitoring in an intensive care unit (ICU).The study challenges the long-standing protocol that calls for intensive monitoring, mostly done in ICUs, for the first 24 hours after tPA infusion to catch bleeding in the brain, a side effect seen in 6 percent of patients treated with the medication.Results show that a relatively simple measure of stroke severity can accurately single out which patients need ICU monitoring and which can be managed outside of a critical care setting in the hospital.”What we saw in this preliminary study was that, after the initial hour-long infusion of tPA, if an intensive care need had not developed, the chance of needing ICU monitoring — including a symptomatic ‘bleed’ — was extremely low for a large majority of patients, namely those with milder strokes,” says Victor Urrutia, M.D., medical director of the Comprehensive Stroke Center at The Johns Hopkins Hospital and head of the research team.Ischemic stroke, caused by a clot in a blood vessel that cuts off blood flow to the brain, is the most common form of stroke and the second leading cause of death for those over 60. In the United States, an estimated 795,000 people suffer a stroke each year. So far, tPA is the only FDA-approved treatment for acute stroke.In a report on the study published online in the journal PLOS ONE, the Johns Hopkins team analyzed data from 153 stroke patients admitted to the emergency departments of The Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center between 2010 and 2013. After taking into account differences in age, sex, race, hypertension, diabetes, atrial fibrillation, kidney function, blood clotting status, use of statin drugs and other health factors, the team says that what emerged as the best predictor of the need for intensive care was a patient’s score on the National Institutes of Health (NIH) Stroke Scale, a trusted measure of stroke severity. The scale is a proven tool administered at the bedside involving 15 measures and observations, including level of consciousness, language ability, eye movements, vision strength, coordination and sensory loss. Scores range from zero to 42, with mild strokes typically registering 10 or lower. The average score for the Johns Hopkins patient group was 9.8.”What we learned is that the majority of our patients with mild strokes required no critical care, and that we are using scarce, specialized resources for intensive monitoring rather than for intensive care,” says Urrutia, an assistant professor of neurology.”If our upcoming, prospective study verifies what we’ve found about those who don’t need to be in the ICU, our patients will benefit, and we will also reduce costs of care.”Urrutia emphasized that critical care is clearly needed for tPa-linked bleeding, stroke-related brain swelling and critical abnormalities in blood pressure or blood sugar.But, he says, “For patients with an NIH Stroke Scale score of less than 10 without a need for transfer to the ICU after the first hour, the risk of a problem occurring later that needed ICU attention was only about 1 percent.”In the follow-up study, which is scheduled to begin this spring, consenting patients with a low stroke scale score and no other apparent need for intensive care will enter a stroke unit with a less rigorous monitoring schedule and increased family visiting time.Patients in the non-ICU setting will be less physically restricted and subjected to fewer sleep interruptions, lowering the risk of ICU-associated delirium and psychological distress. “We expect benefits to extend to the hospital as well, freeing up the ICU staff and beds for sicker patients,” says Urrutia.The financial benefits of the change in protocol could be significant, Urrutia adds. “Present monitoring for patients with tPA is very costly,” he says.

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No clowning around: Juggling sheds light on how we run

Juggling may seem like mere entertainment, but a study led by Johns Hopkins engineers used this circus skill to gather critical clues about how vision and the sense of touch help control the way humans and animals move their limbs in a repetitive way, such as in running. The findings eventually may aid in the treatment of people with neurological diseases and could lead to prosthetic limbs and robots that move more efficiently.The study was published online recently by the Journal of Neurophysiology and will be the cover article in the journal’s March 2014 print edition.In their paper, the team led by Johns Hopkins researchers detailed the unusual jump from juggling for fun to serious science. Jugglers, they explained, rely on repeated rhythmic motions to keep multiple balls aloft. Similar forms of rhythmic movement are also common in the animal world, where effective locomotion is equally important to a swift-moving gazelle and to the cheetah that’s chasing it.”It turns out that the art of juggling provides an interesting window into many of the same questions that you try to answer when you study forms of locomotion, such as walking or running,” said Noah Cowan, an associate professor of mechanical engineering who supervised the research. “In our study, we had participants stand still and use their hands in a rhythmic way. It’s very much like watching them move their feet as they run. But we used juggling as a model for rhythmic motor coordination because it’s a simpler system to study.”Specifically, Cowan and his colleagues wanted to look at how the brain uses vision and the sense of touch to control this type of behavior. To do so, they set up a simple virtual juggling scenario. Participants held a real-world paddle connected to a computer and were told to bounce an on-screen ball repeatedly up to a target area between two lines, also drawn on the monitor. In some trials, the participants had only their vision to guide them. …

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Vertebral augmentation for spinal fractures offers greater survival, overall cost savings

Oct. 17, 2013 — A study of 69,000 Medicare patient records led by Johns Hopkins researchers shows that people with spine compression fractures who undergo operations to strengthen back bones with cement survive longer and have shorter overall hospital stays than those who stick with bed rest, pain control and physical therapy.Although so-called interventional augmentation procedures were initially more expensive than conservative medical management of the fractures, the researchers say the former were associated with lower in-hospital mortality and increased survival compared with non-operative management.”Our results suggest that the beneficial impact of minimally invasive surgery for vertebral compression fractures reaches beyond the acute phase and improves post-discharge survival and morbidity,” says Richard L. Skolasky Jr., Sc.D., associate professor at The Johns Hopkins Hospital’s Department of Orthopaedic Surgery and Spine Outcomes Research Center.Osteoporosis, which mostly affects the elderly, is responsible for more than 700,000 vertebral compression fractures and an estimated 150,000 hospitalizations annually in the United States, Skolasky notes, and can cause significant pain and disability in the elderly. Traditional medical treatment is almost always tried first, while interventional procedures — known as vertebroplasty and kyphoplasty — consist of injecting bone cement through a small hole in the skin into a fractured vertebra. Skolasky noted that vertebral compression fractures are associated with a substantial economic burden, a medical management cost estimated at $13.8 billion in 2001.In a report on the new study, published in the October edition of The Journal of Bone & Joint Surgery, the researchers said that vertebral augmentation procedures not only appear to be associated with greater patient survival than non-operative management, but also that kyphoplasty — which uses balloon inflation to create an opening for the cement — tends to have a more striking association with survival than vertebroplasty.”Treating vertebral compression fractures with vertebral augmentation procedures is associated with acute pain relief and improved mobility, but direct comparisons are limited,” said Skolasky.For the study, Skolasky and his colleagues conducted a “post-hoc” analysis and comparison of information on some 69,000 patients sorted into three categories of fracture care: non-operative, vertebroplasty and kyphoplasty. The team examined differences in survival at six months, one year, two years and three years along with complications, length of hospital stay, charges assessed by the discharging hospital and/or the health care provider delivering services, 30-day readmission rates and repeat procedures.Results showed that the overall survival rate for the entire study population was 77.8 percent at one year and 49.6 percent at three years. The kyphoplasty group had the highest survival rates at one and three years, at 85.2 percent and 59.9 percent, respectively. When examined by age, individuals in the kyphoplasty group consistently had higher survival rates. The study also discovered that patients treated non-operatively on average were hospitalized approximately eight days longer. The total charges for kyphoplasty and vertebroplasty were $12,032 and $7,805 more than those treated non-operatively.Skolasky said that the study showed that there was no statistically significant difference in postoperative infections and neurologic complications between surgical and non-operative patients. …

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Likely causes and treatment strategies for systemic scleroderma identified

Oct. 9, 2013 — Using mice, lab-grown cells and clues from a related disorder, Johns Hopkins researchers have greatly increased understanding of the causes of systemic sclerosis, showing that a critical culprit is a defect in the way certain cells communicate with their structural scaffolding. They say the new insights point the way toward potentially developing drugs for the disease, which affects approximately 100,000 people in the United States.”Until now we’ve had little insight and no effective treatment strategies for systemic sclerosis, and many patients die within a year of diagnosis,” says Hal Dietz, M.D., the Victor A. McKusick Professor of Genetics and Medicine in the Johns Hopkins’ Institute of Genetic Medicine, director of the Smilow Center for Marfan Syndrome Research at Johns Hopkins and Howard Hughes Medical Institute investigator. “Our group created mouse models that allowed us to learn about the sequence of events that leads to the disease’s symptoms, and we hope drugs can be developed that target one or more of these events.” The Dietz team’s results are described in the Oct. 10 issue of Nature.Patients with systemic sclerosis, also known as systemic scleroderma, experience a sudden hardening, or fibrosis, of the skin. For some patients, this hardening occurs only in limited areas, but for others, it quickly spreads across the body and to organs such as the heart, intestines and kidneys. It is this fibrosis of the internal organs that is often fatal.Systemic sclerosis rarely runs in families, Dietz says, making the gene for the disease, if it exists, very difficult to find. Without a known genetic mutation, researchers had not been able to create a genetically altered mouse with which to study the condition. But Dietz’s group was struck by the similarities between systemic sclerosis and a less severe, much rarer condition called stiff skin syndrome (SSS), which does run in families, and they suspected that learning more about SSS would also shed light on systemic sclerosis.In a previous experiment , they pinpointed the genetic mutation responsible for SSS in a gene for a protein called fibrillin-1, which plays a role in other connective tissue disorders. …

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Adding blood pressure drug to standard antibiotics speeds up TB treatment

Aug. 29, 2013 — Infectious disease experts at Johns Hopkins have found, in studies in mice, that a drug better known as a treatment for high blood pressure and headaches effectively speeds up treatment of TB when added to the standard, daily antibiotic regimen. Test animals were cured in four months instead of the usual six.Researchers say that if clinical trials starting later this year in India, a country heavily burdened by the highly contagious lung disease, prove successful, then the shortened treatment time with verapamil, a so-called calcium channel blocker, used in combination with antibiotics isoniazid and rifampin, could make it easier for infected people to complete their drug therapy as prescribed. The experts note that antibiotics for TB do not work if treatment is interrupted or if people stop taking their medication. Improved drug adherence, they say, could also prevent the buildup of drug-resistant strains of TB, caused by Mycobacterium tuberculosis, which is now estimated to kill a million people each year, mostly in the developing world.”Our results show that verapamil is a good drug candidate as an add-on therapy with antibiotics for TB, a global disease in urgent need of new treatment options,” says study senior investigator and infectious disease specialist William Bishai, M.D., Ph.D. Bishai’s team’s latest findings are set to be published in the Sept. 1 edition of the American Journal of Respiratory and Critical Care Medicine.Bishai, a professor at the Johns Hopkins University School of Medicine and its Center for Tuberculosis Research, says that drug treatment options for TB are “too few,” and limited to about a dozen older antibiotics, some with serious side effects. Bishai, who also is a Howard Hughes Medical Institute Lab Head at Johns Hopkins, says verapamil has been around for some 40 years, so its side effects — such as too-low blood pressure — are well-known. He says the clinical trial in India, primarily a safety study to determine a minimum effective dose, will be pivotal in clarifying the drug’s “true potential” as an add-on therapy in TB.Lead study investigator and immunologist Shashank Gupta, Ph.D., says the study results also suggest that verapamil, commonly sold under the brand names Isoptin, Verelan, Calan, Bosoptin and Covera, could be a good drug candidate for combination therapy studies with multidrug-resistant forms of TB.Gupta, a postdoctoral fellow at Johns Hopkins, says verapamil is known to work as an efflux pump inhibitor, making bacteria more susceptible to antibiotics and killing by immune cell macrophages, but whose precise workings remain unknown. He says the research team investigated verapamil’s potential as a TB therapy after another study showed that increased efflux pump action promoted drug tolerance to TB, minimizing antibiotics’ effectiveness.Among the latest study’s other key findings were that verapamil accelerated killing of TB bacteria 10-fold after two months of treatment. …

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Promising therapeutic target for hard-to-treat brain tumor

Aug. 27, 2013 — Johns Hopkins researchers say they have found a specific protein in nearly 100 percent of high-grade meningiomas — the most common form of brain tumor — suggesting a new target for therapies for a cancer that does not respond to current chemotherapy.Importantly, the investigators say, the protein — NY-ESO-1 — is already at the center of a clinical trial underway at the National Cancer Institute. That trial is designed to activate the immune systems of patients with other types of tumors that express the protein, training the body to attack the cancer and eradicate it.”Typically there is a lag time before a laboratory finding like this leads to a clear path forward to help patients. But in this case, since there is already a clinical trial underway, we have a chance of helping people sooner rather than later,” says Gregory J. Riggins, M.D., Ph.D., a professor of neurosurgery at the Johns Hopkins University School of Medicine and the senior author of the study published online in the journal Cancer Immunology Research.In the NCI trial, NY-ESO-1 is found in a much smaller percentage of tumors than Riggins and his team found in high-grade meningioma, suggesting that for the brain cancer, the target would be potentially more significant.Most low-grade meningiomas located in easy-to-reach locations can be treated successfully with surgery and radiation. But more atypical, higher-grade tumors are much more difficult to eradicate and are deadlier.Riggins and his colleagues, including Gilson S. Baia, Ph.D., and Otavia L. Caballero, M.D., Ph.D., set out to find cancer antigens in meningioma. Cancer antigens are proteins expressed in tumors but not in healthy cells, making them good targets for chemical or immune system attack. They looked specifically at 37 cancer/testis (CT) genes, which are not found in normal cells in the body except in germ cells and cells cordoned off in the testicles or, in some cases, ovaries.CT genes are activated, however, in various cancers. …

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Preventive antibiotics for tuberculosis reduce deaths among people with HIV disease

Aug. 15, 2013 — As part of the largest international research effort ever made to combat tuberculosis, a team of Johns Hopkins and Brazilian experts has found that preventive antibiotic therapy for people with HIV lowers this group’s chances of developing TB or dying. Specifically, they found in men and women already infected with HIV that taking isoniazid reduced deaths and new cases of active TB disease by 31 percent, while new cases of TB alone decline by 13 percent.The research team’s findings, to be published in the journal Lancet Infectious Diseases online Aug. 16, stem from what is believed to be the largest expansion of a clinic-based, community health program designed to curb the spread of TB, and the first evidence that such a community-wide effort can be highly effective at preventing people who are co-infected from developing active TB disease.According to senior study investigator and Johns Hopkins infectious disease specialists Richard Chaisson, M.D., his team’s latest study results firmly support broad use of preventive isoniazid therapy for millions of people infected with HIV in Latin American, Asian, and Eastern European countries heavily burdened by TB.Chaisson says TB disease remains the leading cause of death worldwide among those with HIV/AIDS and is epidemic in developing countries with the highest HIV-infection rates. Isoniazid treatment, which costs less than $1 for a full course of therapy, is already recommended by the World Health Organization to prevent TB in people with HIV disease. The policy, however, has not been widely adopted and its broad impact on the HIV-infected community never shown until the Johns Hopkins and Brazilian team’s latest study.All of the 12,816 study participants were eligible for screening for TB infection or active TB disease. Some 1,186 tested positive for TB infection, but did not have symptoms of TB sickness and could start taking 300 milligrams of isoniazid daily for six months. All received routine follow-up care for as little as a few weeks to as long as four years after initially seeking treatment at any of 29 HIV clinics across Brazil, a country hit hard by both infectious diseases. Some 838 deaths occurred during the study, which took four years to complete, and 475 developed TB. Symptoms of active TB disease, indicating the disease has progressed from latent infection, include persistent cough, chest pain, chills, fever, muscle weakness and fatigue.”Our study results show that routine testing for TB and preventive isoniazid therapy works well at the community level in people with HIV disease in curbing the spread of TB and lowering the number who die,” says Chaisson, a professor at the Johns Hopkins University School of Medicine and founding director of its Center for Tuberculosis Research.”People with HIV disease living in all countries with rampant TB should be asking their physicians if they are good candidates for preventive isoniazid therapy,” says Chaisson, who leads the overall global research effort, in support of this study and others, called the Consortium to Respond Effectively to the AIDS/TB Epidemic. …

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Scientists use genome sequencing to demonstrate herbal remedy causes upper urinary tract cancers

Aug. 7, 2013 — Genomic sequencing experts at Johns Hopkins partnered with pharmacologists at Stony Brook University to reveal a striking mutational signature of upper urinary tract cancers caused by aristolochic acid, a plant compound contained in herbal remedies used for thousands of years to treat a variety of ailments such as arthritis, gout and inflammation. Their discovery is described in the Aug. 7 issue of Science Translational Medicine.Aristolochic [pronounced a-ris-to-lo-kik] acid is found in the plant family “Aristolochia,” a vine known widely as birthwort, and while the U.S. Food and Drug Administration first warned of its cancer-causing potential in 2001, botanical products and herbal remedies containing it can still be purchased online. Moreover, the vine has been found to be an environmental carcinogen through the contamination of food supplies of farming villages in the Balkans, where Aristolochia grows wildly in the local wheat fields. For years, scientists have known of some mutations in upper urinary tract cancer patients exposed to the plant toxin. But the genome-wide spectrum of mutations associated with aristolochic acid exposure remained largely unknown.For the current study, the Johns Hopkins and Stony Brook team used whole-exome sequencing on 19 Taiwanese upper urinary tract cancer patients exposed to aristolochic acid, and seven patients with no suspected exposure to the toxin. The technique scours the exome, part of the human genome that contains codes for functional proteins and can reveal particular mutations, in this case, those associated with cancer.”Genome-wide sequencing has allowed us to tie aristolochic acid exposure directly to an individual getting cancer,” Kenneth Kinzler, Ph.D., professor of oncology in the Johns Hopkins Kimmel Cancer Center’s Ludwig Center for Cancer Genetics and Therapeutics. “The technology gives us the recognizable mutational signature to say with certainty that a specific toxin is responsible for causing a specific cancer. …

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New insight into how brain ‘learns’ cocaine addiction

Aug. 1, 2013 — A team of researchers says it has solved the longstanding puzzle of why a key protein linked to learning is also needed to become addicted to cocaine. Results of the study, published in the Aug. 1 issue of the journal Cell, describe how the learning-related protein works with other proteins to forge new pathways in the brain in response to a drug-induced rush of the “pleasure” molecule dopamine. By adding important detail to the process of addiction, the researchers, led by a group at Johns Hopkins, say the work may point the way to new treatments.”The broad question was why and how cocaine strengthened certain circuits in the brain long term, effectively re-wiring the brain for addiction,” says Paul Worley, M.D., a professor in the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine. “What we found in this study was how two very different types of systems in the brain work together to make that happen.” Cocaine addiction, experts say, is among the strongest of addictions.Worley did not come to the problem as an addiction researcher, but as an expert in a group of genes known as immediate early genes, which rapidly ramp up production in neurons when the brain is exposed to new information. In 2001, he said, a European group led by François Conquet of GlaxoSmithKline reported that deleting mGluR5, a protein complex that responds to the common brain-signaling molecule glutamate, made mice unresponsive to cocaine. “That finding came out of the blue,” says Worley, who knew mGluR proteins for their interactions with immediate early genes. “I never would have thought this type of protein was linked to dopamine and addiction, because the functions for it that we knew about up to that point were completely unrelated. …

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Cancer-linked FAM190A gene found to regulate cell division

July 3, 2013 — Johns Hopkins cancer scientists have discovered that a little-described gene known as FAM190A plays a subtle but critical role in regulating the normal cell division process known as mitosis, and the scientists’ research suggests that mutations in the gene may contribute to commonly found chromosomal instability in cancer.In laboratory studies of cells, investigators found that knocking down expression of FAM190A disrupts mitosis. In three pancreatic cancer-cell lines and a standard human-cell line engineered to be deficient in FAM190A, researchers observed that cells often had difficulty separating at the end of mitosis, creating cells with two or more nuclei. The American Journal of Pathology published a description of the work online May 17, which comes nearly a century after German scientist Theodor Boveri linked abnormal mitosis to cancer. Until now, there had been no common gene alteration identified as the culprit for cancer-linked mitosis.”These cells try to divide, and it looks like they succeed, except they wind up with a strand that connects them,” explains Scott Kern, M.D., professor of oncology and pathology at Johns Hopkins University School of Medicine and its Kimmel Cancer Center. “The next time they try to divide, all the nuclei come together, and they try to make four cells instead of two. Subsequently, they try to make eight cells, and so on.” Movies of the process taken by Kern’s laboratory are available on the journal Web site.Kern’s group previously reported that deletions in the FAM190A gene could be found in nearly 40 percent of human cancers. That report, published in 2011 in the journal Oncotarget, and the current one are believed to be the only published papers focused solely on FAM190A, which is frequently altered in human cancers but whose function has been unknown. Alterations in FAM190A messages may be the third most common in human cancers after those for the more well-known genes p53 and p16, Kern says.”We don’t think that a species can exist without FAM190, but we don’t think severe defects in FAM190A readily survive among cancers,” Kern says. “The mutations seen here are very special — they don’t take out the whole gene but instead remove an internal portion and leave what we call the reading frame. We think we’re finding a more subtle defect in human cancers, in which mitosis defects can occur episodically, and we propose it may happen in about 40 percent of human cancers.”Abnormalities in FAM190A may cause chromosomal imbalances seen so commonly in cancers, Kern says. …

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Medications to prevent clots not reaching some patients

June 14, 2013 — Researchers at Johns Hopkins report that hospitalized patients do not receive more than one in 10 doses of doctor-ordered blood thinners prescribed to prevent potentially lethal or disabling blood clots, a decision they say may be fueled by misguided concern by patients and their caregivers.Calling the rate of missed doses “unacceptably high,” the researchers add that hospitalized patients are at a significantly greater risk of developing venous thromboembolism, or VTE, and that preventive blood thinners can prevent it a majority of the time.”There appeared to be a lack of understanding about the risks and benefits of blood thinners among patients and medical staff, even though the research is clear that blood thinners are very effective at preventing blood clots,” says Kenneth M. Shermock, Pharm.D., Ph.D., the director of the Center for Medication Quality and Outcomes at The Johns Hopkins Hospital, and leader of the study published in the journal PLOS ONE. “Blood clots and their resulting effects are the most common cause of avoidable death for hospitalized patients and we’ve got a medication that can prevent most of these events. But too many patients are not benefitting.”Shermock and his colleagues say their study found that 12 percent of ordered doses were not administered to patients, with the most commonly documented reason being patient or family-member refusal (59 percent). Patients were sometimes off the floor getting tests or in surgery when the doses are scheduled to be given.Other research done by Shermock suggests that in some cases nursing staff may have implied to patients that blood thinners are optional. Shermock says it is important to understand the reasons behind this finding and provide more education emphasizing the proven benefits of blood thinners for hospitalized patients.For the PLOS ONE study, Shermock and his colleagues analyzed more than 103,000 VTE prophylaxis doses of unfractionated heparin or enoxaparin ordered for more than 10,500 patients at The Johns Hopkins Hospital between Dec. 1, 2007 and June 30, 2008. Patients from 29 floors were included in the analysis: 11 medicine floors, nine surgery floors, four neurology floors and five intensive care units. They found that while 12 percent of the time ordered doses of blood thinner were not given to the patients, some floors of the hospital had much lower compliance rates.The findings are similar to results previously reported from a Harvard study, but on a much larger scale. At Harvard, in 2012, the researchers went on to provide an individual information session with every patient to explain the value of the blood thinner shots, an intervention that was successful but costly, Shermock says. …

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New mechanism of TB drug resistance identified

June 12, 2013 — Pyrazinamide (PZA) — a frontline tuberculosis (TB) drug — kills dormant persister bacteria and plays a critical role in shortening TB therapy. PZA is used for treating both drug susceptible and multi-drug resistant TB (MDR-TB) but resistance to PZA occurs frequently and can compromise treatment.A recent study, led by researchers at the Johns Hopkins Bloomberg School of Public Health and Huashan Hospital, Fudan University, has identified a new mechanism for PZA-resistance, which provides new insight into the how this mysterious drug works. The study is available online June 12 in the journal Emerging Microbes & Infections.Previously, the Johns Hopkins group identified mutations in the pncA gene and the rpsA gene as the primary causes for PZA resistance. According to the study authors, resistance to PZA is most commonly caused by mutations in the pncA gene encoding enzyme nicotinamidase/pyrazinamidase, which converts the prodrug PZA to the active form pyrazinoic acid (POA), and sometimes associated with mutations in the drug target RpsA (ribosomal protein S1). The active form of PZA, POA, interacts chemically with RpsA to block the trans-translation process, which is essential for bacterium’s survival under stress conditions.However, for unknown reasons, some PZA-resistant TB bacteria lack mutations in pncA or rpsA. The current study suggests that mutations in the panD gene may also be involved. PanD encodes aspartate decarboxylase, which is involved in synthesis of the amino acid β-alanine, a precursor for pantothenate (which is vitamin B5) and co-enzyme A biosynthesis. The panD mutations were identified not only in mutants isolated from in vitro but also in clinical isolates such as in the naturally PZA-resistant bacterium M. canettii strain and in a PZA-resistant MDR-TB strain.”There is significant recent interest in understanding PZA, since it is the only TB drug that cannot be replaced without compromising the efficacy of the therapy. It’s indispensible,” said Ying Zhang, MD, PhD, senior author of the study and professor in the Bloomberg School’s W. …

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Precision-guided needle used to glue shut dangerous and disfiguring blood vessel growth

Nov. 9, 2012 — Using a technique performed at Johns Hopkins but rarely elsewhere, imaging specialists and surgeons have successfully used precision, image-guided technology to glue shut a tangle of abnormal blood vessel growths in a 43-year-old woman’s upper lip, face and nose. Surgery had earlier been ruled out because traditional approaches were considered too risky.

Susan Adams, an accountant from Owings, Md., says her arteriovenous malformation (AVM) had caused a decade of spontaneous nose and lip bleeds that were difficult to control, and that more than a half dozen previous operations had failed to stop the bleeding or facial disfigurement.

Adams’ condition is rare and notoriously difficult to treat. Her AVM had grown -for no known reason — between her upper lip and base of her nose. As it grew, her upper lip and skin above it had bulged out, causing the lower-left side of her face to droop. If left untreated, the condition can lead to life-threatening blood loss from a burst vessel.

For her May 14 procedure, which took about two hours at The Johns Hopkins Hospital, interventional neuroradiologist Monica Pearl, M.D., used an ultrathin needle, precisely guided from the outside in by real-time ultrasound scanning and angiography, to puncture Adams’ facial skin and several of the outermost and largest tangled blood vessels. Once the needle was inside the abnormal blood vessels, which are no more than 1 to 2 millimeters wide, Pearl injected a glue-like substance to block each vessel and cut off the blood supply to any smaller, abnormal branching blood vessels. Pearl says this effectively destroyed the blood vessels making up the AVM.

Pearl was able to select which blood vessels to block using a contrasting dye injected into the tangle immediately prior to the glue-sealing embolization treatment. Using digital subtraction angiography (DSA) — in which computer software removes the images of bones and other organs, showing only the blood vessels — Pearl was able to track reduced blood flow through the AVM after every individual embolization. After three major blood vessels were sealed, blood flow through the tangle became nearly invisible on the DSA images.

Pearl cautioned that the procedure she and her team used is riskier than traditional AVM therapies. Typically, says Pearl, an assistant professor at the Johns Hopkins University School of Medicine who sees an AVM patient about once a week, interventional neuroradiologists and surgeons use the glue sealant to destroy — from the inside — the larger, misshapen arteries, using catheters through major blood vessels elsewhere in the body.

This “inside-in” approach usually lowers the risk of any life-threatening bleeding from burst arteries. However, scarring and postsurgical infections from Adams’ earlier procedures led Pearl and plastic and reconstructive surgeon Amir Dorafshar, M.D., to decide in favor of an “outside-in” approach. Although, other surgeons had ruled Adams situation too risky for further surgery, Pearl and Dorafshar thought success was still possible if Adams AVM could be sealed.

Once the tangle was glued shut, Dorafshar threaded a protective line of sutures around Adam’s facial outgrowth, as protection against any sudden blood loss during Adams’ reconstructive surgery, performed immediately after embolization. In that operation, lasting almost four hours, he cut out the destroyed AVM tangle and put Adams’ upper lip back together, repairing the mucosa, muscle and skin, and re-aligning her nose.

“Our success with this alternative outside-in approach shows our ability to look at medical problems from a different perspective and the potential capabilities for treating what was once considered untreatable,” says Pearl. “People with complex vascular malformations require individualized treatment plans that rely on close collaborations across physician specialties and disciplines.”

According to Pearl and Dorafshar, Adams will need three months to fully recover and will require at least one more operation to repair facial scarring.

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