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The female genital tract is naturally colonized by mixed communities of bacteria, known as the vaginal microbiome. When these communities are dominated by species such as Lactobacillus crispatus, they provide important protective functions in genital health. But overgrowth of certain other bacterial species is linked to a condition known as bacterial vaginosis (BV). BV affects nearly 30% of women around the world, carrying increased risk for sexually transmitted diseases, HIV, and — in pregnant individuals — premature birth. Unfortunately, current antibiotic-based treatments for BV are poorly effective with high rates of recurrence.
One reason for BV recurrence may be that treatment often causes the microbiome to become dominated by a species called Lactobacillus iners instead of by L. crispatus. In a paper published this week in Nature Microbiology, researchers at the Ragon Institute of MGH, MIT and Harvard and colleagues show that L. iners has unique nutritional requirements that distinguish it from L. crispatus, potentially allowing it to be targeted using novel therapeutic strategies.
“L. iners is the most abundant and common vaginal bacterial species worldwide, but it is poorly studied because scientists have had difficulty growing it in lab under conditions used to culture species like L. crispatus,” explains Seth Bloom, MD, PhD, an Instructor in the Infectious Diseases division at Massachusetts General Hospital and Harvard Medical School who was lead author on the study. Bloom and colleagues found that adding the amino acid cysteine to standard Lactobacillus culture media allowed them to grow L. iners strains from samples collected from U.S. and South African women.
Surprisingly, when the researchers analyzed a novel collection of more than 1,200 vaginal Lactobacillus genomes from more than 300 women across four continents, they found that none of the species were able to make their own cysteine. This finding was confirmed in experiments conducted with Ben Woolston, PhD, and Emily Balskus, PhD, at the Harvard Department of Chemistry and Chemical Biology. The team therefore hypothesized that all vaginal Lactobacillus species require external cysteine sources. They measured cysteine concentrations in vaginal fluid samples from South African women with high rates of BV, finding that higher vaginal cysteine levels were linked to Lactobacillus-dominant microbiomes while BV was associated with low cysteine levels.
“The results suggested all vaginal lactobacilli acquire cysteine from their environment, but L. iners’s ability to do so was more limited than other species,” says Bloom. “Indeed, when we looked at the genomes, we saw that all species except L. iners had multiple systems that are predicted to transport cysteine or its oxidized form, cystine.” The team therefore tested effects of compounds known to inhibit cystine uptake, finding that cystine uptake inhibitors selectively blocked growth of L. iners in the lab, but not other Lactobacillus species.
“These findings were exciting because they suggested a way to improve BV treatment by blocking L. iners growth in favor of more health-associated species like L. crispatus,” explains co-author Nomfuneko Mafunda, an MPH candidate at the Harvard T.H. Chan School of Public Health who contributed to this study while working as a technician at the Ragon Institute. To test this idea, Bloom and Mafunda constructed mixed bacterial communities including L. iners, L. crispatus, and various BV-associated bacteria in the laboratory. They then treated the communities with an antibiotic commonly used for BV therapy, with a cystine uptake inhibitor, or a combination of the two. Their results showed that the combination allowed L. crispatus to outcompete other species more effectively than the antibiotic alone.
The researchers believe these results suggest a path to better therapies. “One reason it’s been difficult to develop effective BV treatments is that we haven’t had the correct tools to study the vaginal microbiome in the lab,” says Doug Kwon, MD, PhD, Ragon core member and senior author on the study. “Here, developing the right tool to cultivate L. iners in the lab immediately translated into an important finding that will hopefully lead to improved therapies for BV.”
The team emphasizes that several important questions remain. It isn’t yet clear how L. iners takes up cysteine from its environment, and more potent versions of the inhibitors may need to be developed before the strategy can be used to treat patients. Even so, the study is a promising step forward for this common but difficult-to-treat condition.
Study co-authors include: Seth M. Bloom, Nomfuneko A. Mafunda, Benjamin M. Woolston, Matthew R. Hayward, Josephine F. Frempong, Aaron B. Abai, Jiawu Xu, Alissa J. Mitchell, Xavier Westergaard, Fatima A. Hussain, Nondumiso Xulu, Mary Dong, Krista L. Dong, Thandeka Gumbi, F. Xolisile Ceasar, Justin K. Rice, Namit Choksi, Nasreen Ismail, Thumbi Ndung’u, Musie S. Ghebremichael, David A. Relman, Emily P. Balskus, Caroline M. Mitchell, and Douglas S. Kwon.
The study was supported in part by the National Institutes of Health; the Harvard University Center for AIDS Research (CFAR); the Bill and Melinda Gates Foundation; the Burroughs Wellcome Trust; Vincent Memorial Research Funds; the South African Research Chairs Initiative through the National Research Foundation and the Victor Daitz Foundation; the Thomas C. and Joan M. Merigan Endowment at Stanford; the Harvard Program for Research in Science and Engineering (PRISE); and the Harvard Microbial Sciences Initiative.

Repetitive transcranial magnetic stimulation (rTMS) was associated with a reduction in self-reported cannabis use by up to 60 per cent among people with schizophrenia who have cannabis use disorder (CUD), according to a CAMH-led study just published in the journal NPJ Schizophrenia.
The double-blind study is the first of its kind to investigate the effectiveness of rTMS in treating CUD in people with schizophrenia, and was supported by the U.S. National Institute on Drug Abuse (NIDA) and the CAMH Foundation.
“People with schizophrenia have very high rates of cannabis use disorder compared to the general population, and there is strong evidence that cannabis use worsens psychiatric symptoms and quality of life in these people,” said senior author CAMH clinician scientist Dr. Tony George. “Despite the known harmful effects, there is currently no approved treatment for CUD with or without schizophrenia. These results indicate rTMS may be a safe and effective way to reduce cannabis among people with schizophrenia.”
Until relatively recently, brain stimulation technologies like rTMS were used primarily for treatment-resistant depression. However, studies have now found rTMS to be effective in reducing drug use and cravings for several substance use disorders in the general population.
Study participants were given rTMS treatment at the Temerty Centre for Therapeutic Brain Intervention at CAMH five times a week for four weeks targeting the brain’s the dorsolateral prefrontal cortex (DLPFC), which is associated with the brain’s reward system and executive function.
Those who were given rTMS reported a reduction in cannabis use by up to 60 per cent after 28 days as well as reduced cravings, compared to controls receiving sham rTMS.
The authors state that one of the reasons there is currently no effective treatment for CUD in people with schizophrenia is that people with schizophrenia or other mental illnesses are usually excluded from CUD clinical trials. Dr. George says that CAMH is uniquely positioned to do this kind of research:
“In addition to our ability to conduct clinical trials with brain stimulation at the Temerty Centre, CAMH also has one of the largest schizophrenia outpatient clinics in North America as well as state-of-the-art addiction treatment programs,” said Dr. George. “All those factors make CAMH one of the few places in the world that can lead a study like this.”
“It was a difficult study to recruit for given the intensity of time commitment required by patients,” said study lead author Dr. Karolina Kozak Bidzinski. “However, the awareness patients had of the negative effects cannabis was having on their lives, the expected benefits of reducing their use and noticing the various positive outcomes that would surface throughout the duration of the trial, enabled such a high number of patients to complete the study. Hopefully this work paves the way for more research into investigating the effects of rTMS as a treatment for cannabis use disorder in people with schizophrenia.”
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A new study has analysed over 3000 proteins to identify which are causally linked to the development of severe COVID-19. This is the first study to assess such a large number of proteins for their connection to COVID-19. The findings provide insight into potential new targets for approaches to treat and prevent severe COVID-19.
Published in PLOS Genetics and part-funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre, the study used a genetic tool to screen over 3000 proteins. Researchers identified six proteins that could underlie an increased risk of severe COVID-19 and eight that could contribute to protection from severe COVID-19.
One of the proteins (ABO) that was identified as having a causal connection to the risk of developing severe COVID-19 determines blood groups, suggesting that blood groups play an instrumental role in whether people develop severe forms of the disease.
Co-first author Dr Alish Palmos from Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London said: “We have used a purely genetic approach to investigate a large number of blood proteins and established that a handful have causal links to the development of severe COVID-19. Honing in on this group of proteins is a vital first step in discovering potentially valuable targets for development of new treatments.”
Assessing how blood proteins are linked to disease can help understand the underlying mechanisms and identify potential new targets for developing or repurposing drugs. Protein levels can be measured directly from blood samples but conducting this type of research for large numbers of proteins is costly and cannot establish causal direction.
This is where genetics can play a role. Mendelian randomisation, a method of comparing causal relations between risk factors and health outcomes, using large genetic datasets can assess the relationship between genetic variants connected with an exposure (in this case high levels of individual blood proteins) and genetic variants connected with disease outcome (in this case severe COVID-19).

You are probably familiar with the term that some people carry “a lot of extra baggage.” Usually that term refers to that person’s emotional history, but in genetics and our genomes, “extra baggage” can also describe the transposons lurking in our genomes, a historical record of our genomes surviving traumatic invasions during evolution. Transposons are repetitive DNA sequences that have the capability to move (transpose) from one location to another in the genome (an organism’s complete set of genetic instructions)and areconsidered important invaders of our genomes during evolution.
“Typically, when we are young and healthy, our genomes do a good job handling all these transposons, keeping them stored away. But what if during aging or in unhealthy mutants, how does one handle all this ‘extra baggage’ in our genomes?” a question asked by corresponding author Nelson Lau, PhD, associate professor of biochemistry at BUSM and Director of the BU Genome Science Institute.
In a new study in the journal of PLOS GENETICS, researchers from Boston University School of Medicine (BUSM) tested this question of how these mobile genetic elements can accumulate in the genomes of normal and mutant animals during a single life span. Their study used the model organism of fruit flies which have 12 percent of their genome made up of transposons and are a good proxy for humans, where transposons make up over 40 percent of our DNA.
According to the researchers, typically, young animals store away transposons neatly, so they remain organized and quiet. However, some researchers are now seeing transposons becoming activated during animal aging, when the natural processes to silence transposons decline with age. “Slowing the ravages of aging continues to be an important goal of biomedical research, and this study aimed to determine if transposons activated during aging can move and accumulate in older genomes,” says Lau.
The Lau lab team used whole genome sequencing and bioinformatics to show that normal older fruit flies can keep transposons from accumulating in genomic DNA even though the transposon RNAs were still elevated during aging. However, sicker animals with mutations affecting RNA interference pathways appeared to pile up many more of these transposon copies in the genome during aging.
To see if this condition could be treated, the investigators used genetic tricks to improve the RNA interference pathways in flies, this helped the older flies prevent transposon RNA elevation in old age. In addition, they observed increased lifespan in these modified flies, an outcome that is akin to finding a great therapist who can talk you through issues and not letting the “extra baggage” like transposons continue to weigh you down.
Beyond the genome, the BUSM researchers also discovered that transposons could accumulate as extra-chromosomal circular DNAs. These mysterious circles are distinct from the genome and have also been seen to exist in cancer cells. Although genomic transposons only accumulate in mutant flies, these circles may accumulate even in normal flies.
Future efforts by the Lau lab will be to continue finding out how transposon circular DNAs amass during aging; and if the enhancement of RNA interference in older animals can also halt circular DNA in addition to transposon RNA. “Maybe we could all use some good therapy, not only for our emotional state but for our genomes as well,” adds Lau.
This work was supported by NIH grants R01-AG052465, R21-HD088792 and R01-GM135215 to NCL; and Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (DK015602 to E.P.L.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Communication between brain areas is crucial for the brain to correctly process sensory signals and adopt an appropriate behavioural response. Yet, dysfunctions in these communication pathways could be strongly correlated with the onset of schizophrenia. For the first time, a team from the University of Geneva (UNIGE), Switzerland, within the framework of the Synapsy National Centre of Competence in Research, has succeeded in demonstrating this phenomenon in human beings. By carrying out analyses of the brain activity of children, adolescents and young adults with a genetic risk of the disease, the research team has demonstrated that a reduction in the activation of gamma waves, that are known for their role in the proper transmission of information in the brain, was correlated with the emergence of psychotic symptoms even before full-blown disorders appear. This work, published in the American Journal of Psychiatry, makes it possible to envisage a very early diagnosis.
In the mammalian brain, the electrical activity of neurons responds to oscillatory rhythms that can be detected by electroencephalography. The coordinated activation of these different waves, which governs, for example, the processing of sensory inputs or the consolidation of memories, enables the brain to function correctly. “We suspected that gamma waves, the highest frequency of the brain rhythms, play a decisive role in the development of schizophrenia symptoms,” say Stephan Eliez, professor in the Department of Psychiatry, and Christoph Michel, professor in the Department of Basic Neuroscience, who co-directed the research. “However, we still had to confirm that this impaired synchronisation of neural communication pathways observed in mice does indeed exist in humans.”
Genetic predisposition
People with a chromosomal microdeletion 22q11 have a 25 to 30% risk of developing schizophrenia in adulthood. “They are therefore a particularly relevant at-risk population for studying the cerebral development of this disease,” says Valentina Mancini, a doctoral student in Stephan Eliez’s laboratory and the first author of this study. People with schizophrenia often suffer from reduced capacity to process auditory information; in order to detect any disturbance in brain communication, the scientists therefore measured gamma wave activation following an auditory stimulus in 22q11 patients of all ages, compared with people without this microdeletion.
“Children and adolescents at genetic risk of schizophrenic disorders but without visible symptoms showed the same patterns of gamma wave disruption as patients actually suffering from the disease,” explains Vincent Rochas, a scientific collaborator in Christoph Michel’s laboratory. In addition, a linear growth of the gamma-band oscillations was observed in people with no genetic predisposition to schizophrenia, showing a progressive maturation of communication between the cerebral areas during development. “However, this maturation is absent in 22q11 patients, whatever their age, suggesting an abnormal development of circuits underlying neural oscillations in adolescence,” stresses Valentina Mancini.
Intervening as early as possible
The research team also identified a strong correlation between the gamma-band activation deficit and the severity of psychotic symptoms, such as auditory hallucinations, thus confirming the existence of a neurobiological progression of the disease. “Our results confirm that this dysfunction appears very early,” the authors emphasise. “We now want to identify the best time during the child’s development to intervene in relation to this pathological shift.” Moreover, studies on mice show that targeted neuroleptic treatments succeed in correcting neural dysfunctions; in addition, the gamma-band impairments identified here could be restored using techniques of non-invasive neurostimulation targeting the affected brain regions, thus opening the way to completely new therapeutic perspectives for treating an often devastating disease.
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Wearable devices could soon be entirely made of recycled waste materials — and powered by human movement, thanks to a new energy-harvesting device developed at the University of Surrey.
Scientists have unveiled a wrist device made from discarded paper wipes and plastic cups that runs on energy harvested by the wearer’s movements. The prototype device can transmit Morse code, and the team is now focusing on plans to use this technology in smart watches.
Dr Bhaskar Dudem, project lead and Research Fellow at the University of Surrey’s Advanced Technology Institute (ATI), said:
“It won’t be long until we have to ask ourselves which of the items we own are not connected to the internet. However, the current internet-of-things (IoT) revolution highlights the simple fact that our planet doesn’t have the raw resources to continue to make these devices which are in such high demand.
“Our research demonstrates that there is a path to creating sustainable technology that runs on electricity powered by us, the users of that technology.”
Surrey’s device is ‘self-powered’ thanks to materials that become electrically charged after they come into contact with one another. These materials (also known as Triboelectric Nanogenerators (TENGs)) use static charge to harvest energy from movement through a process called electrostatic induction.
The developers believe their energy-harvesting wearable device could be a future game-changer for the consumer, medical and security sectors.
Professor Ravi Silva, Director of ATI at the University of Surrey, said:
“The core mission of the Advanced Technology Institute is to help build a world where clean energy is available to all. Our energy-harvesting technology embodies this key mission, and we stand ready to work with industry to ensure this technology reaches its full potential.”
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They say a picture can convey a thousand words, and researchers have found that using medical imaging technologies that can visualize health may discourage risk-related behaviors more than non-visual information. The meta-analysis, publishing March 3 in the open access journal PLOS Medicine, finds that when individuals undergo an imaging procedure and are shown visual personalized information about their own risk of disease, they may be more likely to reduce risky behaviors.
Non-communicable diseases are estimated to account for over two-thirds of deaths worldwide each year and are linked to behaviors such as smoking, poor diet, and lack of physical exercise. Behavior change can reduce risks and many interventions intend to motivate such change. Researchers are keen to understand whether the growing use of medical imaging technologies could help.
Gareth Hollands and colleagues at the University of Cambridge, UK conducted a meta-analysis of 21 randomized controlled trials involving over 9,000 adult participants. Participants were either shown visual examples of personalized risk information following an imaging procedure, such as computed tomography, ultrasound, or radiography, in addition to health information or advice, or they received health information or advice with no visual feedback. The trials reported on behaviors including smoking, medication use, physical activity, diet, oral hygiene, sun protection, tanning booth use, blood glucose testing, skin self-examination, and foot care.
The strongest evidence was for smoking reduction, a healthier diet, increased physical activity, and increased oral hygiene behaviors. Single studies also reported increased skin self-examination and foot care following visualized feedback. The other behaviors were improved by visual interventions, but results were not statistically significant. The authors conclude that the growth of medical imaging technology could be capitalized on to help people change and reduce disease risks.
Hollands adds, “Medical imaging scans are used ever more widely by healthcare professionals. By gathering together the existing research, this study suggests that showing the scan results to patients to highlight the state of their health could motivate them to behave in a healthier way.”
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Simultaneous measurement of dozens of types of fats in the blood (“lipidomics”) can predict the risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD) years in the future, according to a new study publishing March 3rd in the open-access journal PLOS Biology from Chris Lauber of Lipotype, Germany, and colleagues. Such early prediction through lipidomic profiling may provide the basis for recommending diet and lifestyle interventions before disease develops.
Current assessment of risk for T2D and CVD relies largely on patient history and current risk behaviors, and the levels and ratio of two major blood lipids, high- and low-density cholesterol. But the blood contains over one hundred other types of lipids, which are thought to reflect at least in part aspects of metabolism and homeostasis throughout the body.
To assess whether a more comprehensive measure of blood lipids could increase the accuracy of risk prediction, the authors drew on data and blood samples from a longitudinal health study of over 4,000 healthy, middle-aged Swedish residents, first assessed from 1991 to 1994, and followed until 2015. Using baseline blood samples, the concentrations of 184 lipids were assessed with high-throughput, quantitative mass spectrometry. During the follow-up period, 13.8% of participants developed T2D, and 22% developed CVD.
To develop the lipid-based risk profile, the authors performed repeated training/test rounds on the data, using a randomly chosen two-thirds of lipid data to create a risk model, and then seeing if the model accurately predicts risk in the remaining third. Once the model was developed, individuals were clustered into one of six subgroups based on their lipidomics profile.
Compared to the group averages, the risk for T2D in the highest-risk group was 37%, an increase in risk of 168%. The risk for CVD in the highest-risk group was 40.5%, an increase in risk of 84%. Significant reductions in risk compared to the averages were also seen in the lowest-risk groups. The increased risk for either disease was independent of known genetic risk factors, and independent of the number of years until disease onset.
There are several potentially important implications of these findings. On an individual level, it may be possible to define risk decades before disease onset, possibly in time to take steps to avert disease. Lipidomics, either in combination with genetics and patient history or independent of them, may provide new insights into when and why disease begins. In addition, by identifying those lipids that contribute most to risk, it may be possible to identify new drug candidates.
“The lipidomic risk, which is derived from only one single mass-spectrometric measurement that is cheap and fast, could extend traditional risk assessment based on clinical assay,” Lauber said. In addition, individual lipids in blood may be the consequences of or contribute to a wide variety of metabolic processes, which may be individually significant as markers of those processes. If that is true, Lauber said, “the lipidome may provide insights much beyond diabetes and cardiovascular disease risk.”
Lauber adds, “Strengthening disease prevention is a global joint effort with many facets. We show how lipidomics can expand our toolkit for early detection of individuals at high risk of developing diabetes and cardiovascular diseases.”
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Only one currently authorized antibody treatment retains its activity against all Omicron subvariants, according to new research by scientists at Columbia University and the University of Hong Kong. The study also shows that the effectiveness of mRNA vaccines is reduced against all three subvariants of Omicron.
The findings were published in Nature on March 2 by David D. Ho, MD, director of the Aaron Diamond AIDS Research Center and the Clyde’56 and Helen Wu Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons.
Omicron is a highly transmissible variant of SARS-CoV-2 that has caused the biggest surge in COVID cases so far in many countries. Researchers have identified three subvariants of Omicron that share 21 mutations in the spike protein, and named them BA.1, BA.1.1 and BA.2.
When Omicron was first identified in November 2021, the dominant variant was BA.1. Since December, BA.1 cases have declined, while BA1.1 cases have risen and now make up around 40% of all Omicron cases sequenced globally. The BA.2 subvariant currently represents only 10% of all Omicron cases globally but is increasing in prevalence.
In laboratory experiments, Ho and his team studied the ability of 19 monoclonal antibodies and the sera from individuals immunized with one of two available mRNA vaccines to neutralize the three known subvariants of Omicron.
Consistent with their previous study on the BA.1 variant, the researchers observed a similar loss of neutralization activity against BA.1.1 and BA.2 in blood samples from individuals who had received two mRNA shots. However, the decline in neutralization was less prominent in blood samples from individuals who had received three mRNA shots, reinforcing the importance of booster shots for sustaining immunity.
In neutralization experiments, all three variants exhibited a strong resistance to most of the monoclonal antibodies tested. Of 19 antibodies, 17 were ineffective against the BA.2 subvariant. The researchers found that bebtelovimab, the latest monoclonal antibody to receive FDA Emergency Use Authorization, is the only currently available antibody therapy that can adequately treat all three Omicron subvariants.
“The emergence of new variants is narrowing our treatment options and challenging the effectiveness of our current vaccines,” says Ho. “It is critical that we don’t relax prematurely and continue to devise novel strategies to contain this ever-evolving pathogen.”
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In a new study published in JAMA Open, University of Minnesota Medical School researchers found that, during the extenuating circumstances of an emerging pandemic, grouping patients together in one area or facility was successful in providing high-quality care and containing infectious patients.
Called cohorting, this patient care model was implemented by M Health Fairview early in the pandemic when little was known about how to effectively treat patients with COVID-19.
“This study highlights the academic and clinical expertise of the M Health Fairview system to deliver outstanding medical care to the people of Minnesota,” said Dr. Greg Beilman, a critical care surgeon at the U of M Medical School and was a co-lead of the M Health Fairview COVID-19 response team. “In this study we demonstrated our ability to rapidly bring new developments in science to the patient’s bedside and improve outcomes for patients affected by this frequently dire disease.”
Because every person being treated in the cohorts had COVID-19, frontline healthcare workers quickly became well-versed in COVID-19 care. These experienced specialists worked side by side with academic physicians who were translating the latest medical research into new solutions they could apply in real time to patient care. COVID-19 patients had access to leading-edge clinical trials, internal COVID-19 testing capabilities, and innovative technology.
The study found that dedicated COVID-19 units in Minnesota were associated with a 2% overall improvement in in-hospital survival rates when patients were properly matched for severity of illness. Complications associated with COVID-19 were significantly better in this group as was the rapid implementation of new care processes by health care providers.
“The opportunity to care for patients at our COVID-19 cohort hospitals was a shining light in a dark time for many of us,” said Dr. Andrew Olson, medical intensivist at the U of M Medical School and medical director of COVID hospital medicine at M Health Fairview. “We watched our colleagues develop expertise, conduct research and care for one another while staying healthy in a challenging time.”
The research team hopes the cohorting method could be implemented when there are outbreaks of infectious diseases, like viral pneumonia. This is due to the fact that the framework helps provide infectious patients the best care during times of rapid learning in scientific research.
“As the pandemic progressed, we had broad availability of personal protective equipment, vaccinations, and more health care workers developed familiarity with treatment of COVID-19,” said Dr. Beilman. “These developments combined with the fact that the incidence of COVID decreased last year — this care model was no longer necessary.”
Researchers plan to further study which patients benefit most from care at such facilities, as well as evaluate the experience for those healthcare professionals who work in them.
This research was funded by U of M Medical School, the Agency for Healthcare Research and Quality, Patient-Centered Outcomes Research Institute, and the National Institutes of Health’s National Center for Advancing Translational Sciences. Additional support for MN-LHS scholars is offered by the U of M Office of Academic Clinical Affairs and the School of Public Health.
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Materials provided by University of Minnesota Medical School. Original written by Kat Dodge. Note: Content may be edited for style and length.