Culture

Ochre, one of Earth's oldest naturally occurring materials, was often used as a vivid red paint in ancient rock art known as pictographs across the world. Despite its broad use throughout human history and a modern focus on how the artistic symbolism is interpreted, little research exists on the paint itself and how it was produced.

Now, scientists led by Brandi MacDonald at the University of Missouri are using archaeological science to understand how ochre paint was created by hunter-gatherers in North America to produce rock art located at Babine Lake in British Columbia. The study was published in Scientific Reports, a journal of Nature.

"Ochre is one of the only types of material that people have continually used for over 200,000 years, if not longer," said MacDonald, who specializes in ancient pigments. "Therefore, we have a deep history in the archeological record of humans selecting and engaging with this material, but few people study how it's actually made."

This is the first study of the rock art at Babine Lake. It shows that individuals who prepared the ochre paints harvested an aquatic, iron-rich bacteria out of the lake -- in the form of an orange-brown sediment.

In the study, the scientists used modern technology, including the ability to heat a single grain of ochre and watch the effects of temperature change under an electron microscope at MU's Electron Microscopy Core facility. They determined that individuals at Babine Lake deliberately heated this bacteria to a temperature range of approximately 750°C to 850°C to initiate the color transformation.

"It's common to think about the production of red paint as people collecting red rocks and crushing them up," MacDonald said. "Here, with the help of multiple scientific methods, we were able to reconstruct the approximate temperature at which the people at Babine Lake were deliberately heating this biogenic paint over open-hearth fires. So, this wasn't a transformation done by chance with nature. Today, engineers are spending a lot of money trying to determine how to produce highly thermo-stable paints for ceramic manufacturing or aerospace engineering without much known success, yet we've found that hunter-gatherers had already discovered a successful way to do this long ago."

The University of Barcelona (UB) and Hospital Clínic de Barcelona collaborate with Boehringer Ingelheim Inc. to improve the efficiency of nintedanib, an antiangiogenic and antifibrotic drug, for the treatment of lung cancer. This public-private collaboration enabled researchers identify molecular mechanisms underlying the lack of efficiency of this drug in squamous cell carcinoma, a sub-type of non-small cell lung cancer, and the important role of smoking in this lack of effectivity.

These results, published in the journal Cancer Research, could have implications in the design of new therapeutic strategies to expand the clinical benefits of the drug to a larger spectra of patients with lung cancer, the main cause of cancer-related death regarding cancer worldwide. The 17th of November was the international day for this pathology.

The study is led by Jordi Alcaraz, tenure track-2 lecturer from the Department of Biomedicine of the Faculty of Medicine and Health Sciences of the University of Barcelona,with the collaboration of the team of Noemí Reguart, head of the Unit of Thoracic Tumours of Hospital Clínic de Barcelona and researcher at the August Pi i Sunyer Biomedical Research Institute (IDIBAPS). The Bosch i Gimpera Foundation as Research Results Transfer Office (OTRI) of the University of Barcelona has been in charge of the contract management. The project has been made possible thanks to the generous funding provided by Cellex Foundation, the Spanish Ministry of Science, Innovation and Universities (with co-funding from the EU FEDER funds), and the Spanish Association against Cancer (AECC).

Nintedanib is a drug developed by Boehringer Ingelheim which showed therapeutic benefits in patients with advanced lung adenocarcinoma. Its action mechanism is based on the inhibition of receptors involved in the formation of new vessels (angiogenesis) and fibrosis, which drive tumor progression.

Previous studies within this collaboration reported that this drug is efficient to treat advanced lung adenocarcinoma but not squamous cell carcinoma. To identify the causes of the differences between the two main sub-types of non-small cell lung cancer, the new study analysed tumor fibrosis (chronic tissue scarring) and the response to the antifibrotic treatment with nintedanib, in cells and tissue samples from lung cancer patients, provided by Hospital Clinic, the Respiratory Diseases Networking Biomedical Research Centre (CIBERES) and the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). The study used pre-clinical cell culture models that are unique in Spain, which allow the interaction between the two most abundant cell within a tumor: cancer cells and fibroblasts, a type of non-malignant cells that surround them and are key drivers of tumour progression.

Smoking reduces the drug's efficiency

"The results describe for the first time that tumor fibrosis is higher in adecarcinoma than in squamous cell carcinoma, which causes patients with adenocarcinoma to respond better to treatment with nintedanib. Furthermore, we identify the underlying mechanism: the pro-fibrotic transcription factor SMAD3 in fibroblasts- the main cells that drive fibrosis- is more epigenetically repressed in squamous cell carcinoma than in adenocarcinoma, and this makes patients with squamous cell carcinoma to have less fibrosis and to be resistant to nintedanib", says Jordi Alcaraz, researcher at CIBERES.

The study also identified the key role of smoking in the lack of efficiency of the drug against squamous cell carcinoma. "This is the first time that a study describes how cigarette smoke particles modify epigenetically the SMAD3 gene to ultimately reduce its activity and increase the resistance to the drug", says the researcher says.

A new therapeutic strategy

The results of the study could also have further implications in the design of therapeutical strategies to treat adenocarcinoma with different drug combinations of drugs. "Since fibrosis is a common adverse effect induced by radiotherapy toxicity, our results suggest patients with adenocarcinoma (especially non-smokers) who receive radiotherapy could benefit from antifibrotic drugs such as nintedanib combined with radiotherapy. Likewise -continues Jordi Alcaraz-, since fibrosis is associated with immunosuppression and tumor growth, our results support that patients with adenocarcinoma could benefit from the combination of antifibrotic drugs like nintedanib with immunotherapy".

This public-private agreement results from the commitment of all the involved institutions working on quality research in a special health topic such as lung cancer, and in particular, squamous cell carcinoma, which affects about 30% of patients with this type of cancer. "This is a good example of the important advances that can be obtained through collaborations between the university, the hospital and pharmaceutical companies", stresses Jordi Alcaraz.

Nintedanib

Commercialized as Vargatef, nintedanib combined with docetaxel was the first treatment aimed at advanced lung adenocarcinoma to show a higher average survival per year (12.6 months) after the failure of the initial chemotherapy. It is aimed for the treatment, combined with docetaxel, on patients with locally, recurrent or metastasic advanced non-small cell lung cancer with adenocarcinoma histology, after first-line chemotherapy.

Its clinical efficiency is proved by the results of the LUME-Lung 1 study, carried out in 27 countries with more than 1,300 included patients. This study proved a significant improvement in the survival with the combined treatment of nintedanib with docetaxel1.

A new study finds that while the current United States administration's policies in Africa may appear undeveloped, there are distinct trends and tendencies that have the potential to negatively impact Africa's economic growth.

The study was published in the peer-reviewed academic journal Africa Today. It was co-authored by Francis Owusu, professor and chair of community and regional planning at Iowa State University; Padraig Carmody, associate professor of geography at Trinity College Dublin; and Ricardo Reboredo, Ph.D. candidate at Trinity College Dublin.

The researchers studied the nature and impacts of the Trump administration's policies in Africa, focusing on trade relations, development aid, foreign direct investments (FDI), security and terrorism concerns, and climate change. They also looked at whether China and the United Kingdom will seek to strengthen their relationships in Africa given relative U.S. disengagement.

"Reduced engagement has both real human costs in Africa, in addition to storing up problems for the future," Owusu said. "The general U.S. disengagement with Africa is even more troubling, given the growing importance of Africa's role in global economic and political affairs and the growing interest by other powers in engaging with Africa."

The study found that the Trump administration's approach to Africa involves "selective delinking" from various relations, including aid, trade and investment. This paper delves into the history of the U.S.-Africa relationship, and examines recent policies and events that illuminate current and future globalization impacts on Africa.

The cover for issue 62 of Oncotarget features Figure 7, "Proposed model of the hyperploid pathway as a salvage survival strategy regulated by the G2-M checkpoint," by Yeung, et al.

Subpopulations of tumor cells may exhibit diverging behaviors from the bulk tumor due to an alternate stress response that diverts tumor cells from apoptotic death.

In this study, the researcher identified a salvage survival pathway in which G2-arrested tumor cells bypassed apoptosis and progressed through aberrant mitotic events to then emerge as a distinct subpopulation of viable large hyperploid cells but with uncertain long-term propagation potential.

Dr. Robert Rottapel and Dr. Andras Kapus said "High grade serous carcinoma (HGSC) of tubal-ovarian origin is an aggressive epithelial tumor with poor survival outcomes. Platinum drugs are used as part of first-line therapy and exert genotoxic effects to tumor cells"

For tumor cells lacking a functional G1-S checkpoint such as in high grade serous carcinoma where the retinoblastoma and p53 pathways are perturbed, an arrest in cell cycle at the G2 phase is critical for DNA damage repair.

The entry to mitosis with residual DNA damage often results in mitotic catastrophe-mediated cell death but occasional tumor cells may circumvent mitotic death by failure to complete telekinesis and revert back to a single cell state termed mitotic slippage .

While chemotherapy treatment induces apoptotic cell death in the tumor, there are additional morphologic changes within the treated tumor field that suggest alternate mode of cell death or occasional survival via non-canonical response to treatment.

The cell cycle and DNA ploidy status are then additionally correlated with markers of key cellular programs such as the DNA damage response and G2-M cell cycle checkpoint pathway via immunofluorescence staining.

As this approach analyzes all tumor cells within a population at the single cell level, distinct subpopulational responses to treatment within the bulk tumor cell line can be revealed.

Using this refined technical approach, here we demonstrate that platinum treatment induces nuclear enlargement in the surviving cell population of several HGSC cell line models, and this in-vitro observation resembles closely to the morphologic changes seen in-vivo in patient tumors after neoadjuvant chemotherapy treatment.

The Rottapel/Kapus Research Team concluded, "The efficacy of this pathway to produce viable progenies was low and highly contingent on the initial platinum concentration that generated the hyperploid cells.

Potentially, the coupled process of hyperploidization and de-polyploidization might increase the genomic diversity of the recovering tumor cell line and contribute to acquired platinum resistance."

Full text - https://doi.org/10.18632/oncotarget.27330

Correspondence to - Robert Rottapel - rottapel@uhnresearch.ca and Andras Kapus - andras.kapus@unityhealth.to

Journal

Oncotarget

DOI

10.18632/oncotarget.27330

CAMBRIDGE, MA -- When your immune system is exposed to a vaccine, an allergen, or an infectious microbe, subsets of T cells that can recognize a foreign intruder leap into action. Some of these T cells are primed to kill infected cells, while others serve as memory cells that circulate throughout the body, keeping watch in case the invader reappears.

MIT researchers have now devised a way to identify T cells that share a particular target, as part of a process called high-throughput single-cell RNA sequencing. This kind of profiling can reveal the unique functions of those T cells by determining which genes they turn on at a given time. In a new study, the researchers used this technique to identify T cells that produce the inflammation seen in patients with peanut allergies.

In work that is now underway, the researchers are using this method to study how patients' T cells respond to oral immunotherapy for peanut allergies, which could help them determine whether the therapy will work for a particular patient. Such studies could also help guide researchers in developing and testing new treatments.

"Food allergies affect about 5 percent of the population, and there's not really a clear clinical intervention other than avoidance, which can cause a lot of stress for families and for the patients themselves," says J. Christopher Love, the Raymond A. and Helen E. St. Laurent Professor of Chemical Engineering and a member of MIT's Koch Institute for Integrative Cancer Research. "Understanding the underlying biology of what drives these reactions is still a really critical question."

Love and Alex K. Shalek, who is the Pfizer-Laubach Career Development Associate Professor at MIT, an associate professor of chemistry, a core member of MIT's Institute for Medical Engineering and Science (IMES), and an extramural member of the Koch Institute, are the senior authors of the study, which appears today in Nature Immunology. The lead authors of the paper are graduate student Ang Andy Tu and former postdoc Todd Gierahn.

Extracting information

The researchers' new method builds on their previous work developing techniques for rapidly performing single-cell RNA sequencing on large populations of cells. By sequencing messenger RNA, scientists can discover which genes are being expressed at a given time, giving them insight into individual cells' functions.

Performing RNA sequencing on immune cells, such as T cells, is of great interest because T cells have so many different roles in the immune response. However, previous sequencing studies could not identify populations of T cells that respond to a particular target, or antigen, which is determined by the sequence of the T cell receptor (TCR). That's because single-cell RNA sequencing usually tags and sequences only one end of each RNA molecule, and most of the variation in T cell receptor genes is found at the opposite end of the molecule, which doesn't get sequenced.

"For a long time, people have been describing T cells and their transcriptome with this method, but without information about what kind of T cell receptor the cells actually have," Tu says. "When this project started, we were thinking about how we could try to recover that information from these libraries in a way that doesn't obscure the single-cell resolution of these datasets, and doesn't require us to dramatically change our sequencing workflow and platform."

In a single T cell, RNA that encodes T cell receptors makes up less than 1 percent of the cell's total RNA, so the MIT team came up with a way to amplify those specific RNA molecules and then pull them out of the total sample so that they could be fully sequenced. Each RNA molecule is tagged with a barcode to reveal which cell it came from, so the researchers could match up the T cells' targets with their patterns of RNA expression. This allows them to determine which genes are active in populations of T cells that target specific antigens.

"To put the function of T cells into context, you have to understand what it is they're trying to recognize," Shalek says. "This method lets you take existing single-cell RNA sequencing libraries and pull out relevant sequences you might want to characterize. At its core, the approach is a straightforward strategy for extracting some of the information that's hidden inside of genome-wide expression profiling data."

Another advantage of this technique is that it doesn't require expensive chemicals, relies on equipment that many labs already have, and can be applied to many previously processed samples, the researchers say.

Analyzing allergies

In the Nature Immunology paper, the researchers demonstrated that they could use this technique to pick out mouse T cells that were active against human papilloma virus, after the mice had been vaccinated against the virus. They found that even though all of these T cells reacted to the virus, the cells had different TCRs and appeared to be in different stages of development -- some were very activated for killing infected cells, while others were focused on growing and dividing.

The researchers then analyzed T cells taken from four patients with peanut allergies. After exposing the cells to peanut allergens, they were able to identify T cells that were active against those allergens. They also showed which subsets of T cells were the most active, and found some that were producing the inflammatory cytokines that are usually associated with allergic reactions.

"We can now start to stratify the data to reveal what are the most important cells, which we were not able to identify before with RNA sequencing alone," Tu says.

Love's lab is now working with researchers at Massachusetts General Hospital to use this technique to track the immune responses of people undergoing oral immunotherapy for peanut allergies -- a technique that involves consuming small amounts of the allergen, allowing the immune system to build up tolerance to it.

In clinical trials, this technique has been shown to work in some but not all patients. The MIT/MGH team hopes that their study will help identify factors that could be used to predict which patients will respond best to the treatment.

"One would certainly like to have a better sense of whether an intervention is going to be successful or not, as early as possible," Love says.

This strategy could also be used to help develop and monitor immunotherapy treatments for cancer, such as CAR-T cell therapy, which involves programming a patient's own T cells to target a tumor. Shalek's lab is also actively applying this technique with collaborators at the Ragon Institute of MGH, MIT and Harvard to identify T cells that are involved in fighting infections such as HIV and tuberculosis.

Berkeley -- Teen girls in South Africa face an extraordinary threat of HIV: By the time they reach adulthood, one in four South African girls will have contracted the virus, and most are first infected during adolescence.

Experiencing depression puts these girls at even higher risk of HIV infection, reveals analyses led by researchers at the University of California, Berkeley, and based on a longitudinal study led by colleagues at the University of North Carolina and the University of the Witwatersrand, South Africa.

The findings, which appear online in the American Journal of Epidemiology, suggest that interventions targeted at improving mental health among adolescent girls may help stem the spread of HIV in South Africa and throughout the rest of sub-Saharan Africa.

"We've known that depression and HIV go together for decades, but no one has known which way the arrow goes: Does depression lead to HIV or does HIV lead to depression?" said Jennifer Ahern, professor of epidemiology at UC Berkeley and senior author on the study. "Probably it goes both ways, but we were able to show that, at least in this population, the arrow certainly goes one way, which is depression leads to HIV. This could have important implications for where interventions might lie."

As part of the study, the team looked at which aspects of teens' social lives and behaviors might explain the relationship between depression and HIV incidence. Teen girls who experienced symptoms of depression were later more likely to report not having close relationships with their parents, and having a partner who would hit her if she asked him to wear a condom. These factors appeared to be part of the pathway to contracting HIV.

"Partner violence in response to condom negotiations, and a lack of parental monitoring, had the strongest association with both depression and HIV, which indicates that the majority of the relationship between depression and HIV may be influenced through those factors," said Dana Goin, a postdoctoral scholar in the Department of Obstetrics, Gynecology, and Reproductive Sciences at the University of California, San Francisco, and lead author of the study.

"The results illustrate how so much of infection among this population has to do with structural factors," said Goin, who completed the work as a PhD candidate in epidemiology at UC Berkeley.

The study drew on data collected from 2,533 women between the ages of 13 and 21 living in rural Mpumalanga Province, South Africa. Each teen was screened for symptoms of depression at the beginning of the study, and then tested for HIV annually for six years.

A little more than 18% of the adolescents had depression at the outset of the study -- about twice the national average of South Africa. Of those with depression, nearly 11 percent went on to contract HIV, while only 6.5% of those without depression eventually became infected.

While a previous study has shown that depression can lead to higher incidence of HIV in men who have sex with men in the U.S., this is the first study to examine the relationship among girls and young women in sub-Saharan Africa.

Though residents in rural South Africa have limited access to mental health services, Ahern and Goin's collaborators at Oxford University and at the University of the Witwatersrand in South Africa are currently working to develop community-based interventions that can help identify and support girls who are experiencing depression.

"There is increasing evidence that proven psychological treatments for depression, such as behavioral activation, can be delivered by lay counsellors and community healthcare workers, which provides a feasible way of delivering treatment for depression in the community," said Alan Stein, a professor of child and adolescent psychiatry at the University of Oxford. "There is also the possibility of delivering these kinds of treatments using the internet or mobile phones, with the support of phone calls from peer mentors, and this is something we are working on."

"Many low- and middle- income settings, including much of Africa, lack skilled mental health personnel," added Kathleen Kahn, a professor and senior scientist at the Medical Research Council / Wits University Rural Public Health and Health Transitions Research Unit (Agincourt) at the School of Public Health, University of the Witwatersrand and co-author on the paper. "Interventions that can be delivered by non-specialist workers -- lay health workers or community health workers -- and that are appropriate across different cultures should be vigorously pursued. This is what our work now focuses on."

When we pass through an art gallery, what determines our idea of beauty? A University of Sydney study of how people rate the aesthetics of each artwork shows part of our aesthetic assessment is due to the painting you saw a few moments before.

The research, led by PhD student Ms Sujin Kim in the School of Psychology, is published in the Journal of Vision. It shows that we don't appreciate every painting in isolation. Instead, we carry a bias from the artwork just seen.

This bias is not the contrast effect you might intuitively think. A beautiful painting does not make the next one look less attractive but makes it more attractive.

The study, completed under the supervision of Professor David Alais from the University of Sydney and Professor David Burr from the University of Florence, Italy, involved presenting a sequence of 40 paintings to 24 observers who were asked to rate each one using a slider to indicate how aesthetically appealing or attractive it was. The paintings were depicting scenery or still life.

"While it is often said that beauty is in the eye of the beholder, this is not the whole story - it partly depends on what was recently seen," Professor Alais said.

The first question the 24 observers were asked to respond to was whether they rated each painting independently of what they had just seen. To do this, the sequence was presented 20 times with each run having a different random order. In this way, a given painting was rated 20 times, but with a different random sequence preceding it. The data was clear: observers don't rate each painting consistently but are biased by what they just saw.

"Many people naively suppose a kind of 'contrast effect' whereby a painting may look more attractive if it follows an unattractive painting," Professor Alais said. "The surprising result was that the bias was a positive one: paintings were rated higher following an attractive painting, or lower, following unattractive ones."

The research refers to this effect as "serial dependence", which describes a systemic bias towards recent past experience. Previous studies have found, many stimulus attributes - including orientation, numerosity, facial expression and attractiveness, and perceived slimness - are systematically biased towards recent past experience.
"Perhaps art curators have known all along about the bias towards the recent past," Professor Alais said. "They often keep the best pieces for last and build up to it. Our study shows this would ensure an accumulating effect and guarantee a big finish."

Researchers of Sechenov University together with their colleagues from several Russian institutes studied the dynamics of microtubules that form the basis of the cytoskeleton and take part in the transfer of particles within a cell and its division. The computer model they developed describes the mechanical properties of protofilaments (longitudinal fibers that compose microtubules) and suggests how they assemble and disassemble. All the details of the study can be found in PLOS Computational Biology.

Microtubules are long hollow cylinders with walls consisting of tubulin molecules arranged helix-wise. Each cycle contains 13 pairs of α- and β-tubulin, so a microtubule is composed of 13 longitudinal fibers, protofilaments. Microtubules grow by addition of tubulin from the cytoplasm. The protein binds more actively to one end (plus-end) of the microtubule and dissociates from the other one (minus-end) quicker. Both processes take place simultaneously, but their rate changes: when the concentration of tubulin is sufficient, microtubules grow faster than degrade, and when the concentration is low - vice versa. Between the phases of growth and shrinking there is a period of stability, but it is very short.

Though the mechanisms of microtubule's growth and shortening are well-studied, there are still quite a few questions about how the structure and properties of tubulin change. It is known that both molecules of tubulin (α- and β-tubulin) are connected to a molecule of guanosine triphosphate (GTP). GTP of β-tubulin can hydrolyse and turn into guanosine diphosphate (GDP) that causes the double tubulin molecule (dimer) to dissociate from a microtubule. The authors of the paper tried to understand how the properties of tubulin dimers and protofilaments depend on GTP hydrolysis and what provides the difference between plus- and minus-ends of microtubules. Above all, microtubules take part in cell division, and studies of these mechanisms will contribute to the search for yet unknown ways to suppress the replication of cancer cells. In particular, microtubules serve as molecular targets for an important anti-tumour drug, paclitaxel, that inhibits microtubule disassembly.

Existing studies offer several models of possible changes in protein structure taking place upon GTP hydrolysis: a slight curving of tubulin dimers or weakening of longitudinal bonds between dimers without significant changes in their shape. Some researchers also suggest that hydrolysis may affect interactions between neighbouring protofilaments. According to the authors, it was impossible to prove or refute any of these claims for a long time because of the lack of precise experimental data. In this research they verified the first hypothesis and computed the 'behaviour' of molecules using the latest of available experimental structures obtained by cryo-electron tomography. They examined bonds between dimers as well as between α- and β-tubulin within them.

Scientists modelled the bending of the tubulin dimer and the whole protofilament, with GTP and GDP bound to them, throughout one millisecond, watching the angle and direction of the curvature and assessing the strength of bonds within and between dimers. The results showed that protofilaments with GTP and GDP-bound tubulin were bent almost to the same extent, so the first hypothesis was disproved. But it turned out that GTP influences the flexibility of the bonds between dimers: protofilaments made of tubulin connected with GTP were much more bendable compared with those containing GDP.

Using the revealed difference in bond rigidity between GTP and GDP-connected protofilaments, the authors concluded that more flexible bonds ease the straightening of protofilaments and thus facilitate the assembly of the microtubule.

'Based on simulations, we developed a simple model of dynamic instability of microtubules, i.e. their assembly and disassembly. A deeper understanding of this process on the molecular level would enable a targeted development of medicines able to affect the stability of microtubules and thus prevent the reproduction of tumour cells', said Philipp Orekhov, co-author of the paper and senior scientist at the Institute for Personalized Medicine, Sechenov University.

While the diagnoses and treatment of sport-related concussion have well-established guidelines and protocols, a new study from UBC's Okanagan campus is looking at what has previously been an understudied group--women survivors of intimate partner violence (IPV).

Their hope is to develop a simple screening tool to help front-line services, like women's shelters, identify traumatic brain injury (TBI) earlier, says Paul van Donkelaar, lead researcher and professor with the School of Health and Exercise Sciences.

"It is widely known survivors of intimate partner violence face many short- and long-term consequences from abuse which can have profound impacts on both their mental and physical health," says van Donkelaar. "But there is currently very little direct evidence for the potential link between this violence and traumatic brain injury-induced brain dysfunction."

Despite the abundance of research and public awareness around brain injury in athletes, van Donkelaar says traumatic brain injuries suffered by survivors of IPV are largely ignored. In fact, his most recent research, which is hoping to establish the incidence and effects of TBI on these women, is only the fourth study he knows of that deals specifically with this issue.

"IPV happens behind closed doors and usually there are no witnesses--if there are witnesses they are generally the children and they are traumatized," says van Donkelaar, adding that if a survivor does seek medical help after an attack it is often for other traumatic injuries. "In many cases, survivors of IPV don't necessarily know they have had a traumatic brain injury and yet they are suffering from chronic symptoms including headaches, dizziness, and difficulty remembering," he says.

"If a brain injury is diagnosed, it might be several months or even years after the initial damaging blow took place. And was it caused by one blow, multiple attacks over several months, or from being shaken or even strangled?"

While diagnosis is a challenge, there also remains a social stigma with IPV. Van Donkelaar says many women who do seek medical help, may not tell the truth when asked how the injury occurred. For these reasons alone, van Donkelaar and his research team, including former UBCO postdoctoral fellow Jonathan Smirl, want to make concussion assessments and care for survivors of IPV accessible and straightforward.

"Although the health care system is a good place for TBI diagnoses in the context of IPV, many survivors do not feel comfortable accessing care in this manner so this leaves staff at women shelters as the first line of defense," says Smirl. "Yet these staff members aren't necessarily aware TBI can be part of their client's experience and currently do not have appropriate screening tools available to them."

For this latest research, the team used two brain injury questionnaires--the Brain Injury Severity Assessment tool (BISA) and the Sport Concussion Assessment Tool (SCAT5)--to get a better sense of the symptoms experienced by survivors of IPV. Eighteen women who had experienced IPV took the part in the study.

The research, published in Brain Injury, determined that by using the BISA test, which asks questions about symptoms resulting from episodes of IPV, more brain injuries were reported by the survivors. The study determined that each of the participants have suffered at least one previous TBI, and most had suffered many.

"It's estimated that several hundred thousand Canadian women a year experience a TBI, an even greater number than hockey or football players," says Smirl. "And yet, due to the perceived stigma around IPV, many of these women don't seek medical support. Unfortunately, living in this situation is their normal, waking up in a daze because she was punched again is her normal. Not only is it going undiagnosed, it's going untreated."

The findings from the current investigation can help develop TBI-informed screening tools to help front-line staff at women's shelters identify a brain injury as a possible factor in the symptoms experienced by IPV survivors.

"What we're hoping to do is implement a simple informed screening tool, just a few questions that front-line staff can ask which can help reveal whether a woman has potentially experienced an IPV-related TBI," he says. "We will then be able to use it as a means to refer them to appropriate supports in the community."

Van Donkelaar says providing these practical support resources to IPV survivors will improve their chances of breaking the cycle and enable them to move forward into an abuse-free future for themselves and their children.

MAYWOOD, IL - The past 25 years have seen a significant increase in student participation in high school athletics. Studies have revealed that 2 million injuries, 500,000 doctor visits and 30,000 hospitalizations occur each year among high school athletes. This has led to strong recommendations from the National Athletic Trainers' Association (NATA), the American Academy of Family Physicians and the American Medical Association for physician sideline coverage at high school games and practices.

In addition to this recommendation, providing proper training to athletic directors and coaches, having a defibrillator on the sidelines, having a concussion protocol in place and teaching proper tackling progressions can all impact the overall health and safety of student athletes.

Researchers at Loyola Medicine recently completed a follow-up study to reassess the state of medical sideline coverage during football games and practices at the 99 Chicago public high schools. The team is led by Nathaniel Jones, MD, sports medicine specialist, who collaborated with Pietro Tonino, MD, Chief of Sports Medicine, who published a similar study in 2003.

Through the use of an online survey, researchers requested information about the personnel available to assess medical problems at home football games and at practices as well as CPR and first aid certification of these Chicago public high school staffers.

Of most concern are concussions, catastrophic events, cervical spine injuries and sudden cardiac events, for which players' outcomes can be impacted by having a physician present. "The impact," Dr. Jones says, "is that immediate and appropriate medical care saves lives. Properly trained medical professionals know when to prioritize a serious injury.

For instance, head injuries should be handled differently and more urgently than an ankle sprain." Dr. Tonino notes that concussions are a significant issue. "If an athlete gets a concussion that is not diagnosed, this may impact his or her performance at school which can have long-term effects," he says.

Sixty-six Chicago public high schools responded to the recent survey, revealing a greater proportion of schools with athletic trainers and ambulances on the sidelines at home football games as compared to responses in 2003. By contrast, a smaller proportion of responding schools had a physician or paramedic on the sidelines.

Additionally, the proportion of head coaches certified in CPR and first aid decreased. "Practices are a big issue," says Dr. Tonino, "just as you can get a concussion in a game, the same thing can happen in practice. Often the coach is the only person there. It's important that the coach has some training and basic knowledge."

With regard to practical implications, Dr. Jones notes that Chicago public high schools share stadiums throughout the city. Ideally, Chicago medical centers would commit attending physicians, fellows and residents in primary care and sports medicine to cover stadiums during football games. "If Chicago's medical centers agreed to share coverage, we could offer comprehensive coverage for Chicago public high school student athletes," says Dr. Jones.

Education is also a key component. To that end, Loyola Medicine offers a sports medicine update conference annually, which shares the latest research in sports medicine, updates on best practices, gender differences in sports injuries, and education on a variety of injuries that can occur on the field. This conference is available to medical professionals, coaches and other school staff.

"Sports keep kids out of trouble," says Dr. Jones. "We don't want students to stop playing sports, but rather, we want athletes to have access to appropriate medical care during games and practices. We want parents and students to know the risks of contact sports, but also know that sports are important for kids to participate in. It keeps kids healthy, teaches teamwork, and kids learn how their performance effects the whole team."

It is generally known that viruses, with their cell-invading capabilities, can be responsible for a number of different cancers. What is less broadly discussed are the cancer-causing capabilities of bacteria, or the processes by which they may cause malignancy.

In a review article appearing in the November 18 issue of Trends in Molecular Medicine, University of North Carolina at Charlotte, cancer biologists Pinku Mukherjee and Mukulika Bose discuss a mechanism that, they suggest, may implicate bacterial infections in a wide variety of cancers - a cause that science has yet to fully understood.

The article, "Microbe - MUC1 Crosstalk in Cancer-Associated Infections," makes the case for the likely implication of microbial (especially bacterial) interactions with the glycoprotein known as MUC1 in cancers involving epithelial cells, including cancers of the colon, lungs, stomach, liver and pancreas.

Epithelial cells are cells that are frequently specialized for absorption or secretion purposes, and to form linings or barriers in organs, including the intestines, lungs, stomach, liver and reproductive organs. MUC1 is a "transmembrane" protein - extending outside, through and inside the cell membrane to the cytoplasm - and is present in nearly all glandular epithelial cells. It is one of a group of proteins known as "mucins" for their involvement in protective mucous layers, whose gel-forming features are caused by sugar molecules coating part of the protein's length ("glycosolation"). The sugars, essentially, interact with water molecules, creating a slippery, slimy barrier, protecting cell layers against pathogens and environmental damage.

Mukherjee, Irwin Belk Distinguished Professor of Cancer Research and chair of UNC Charlotte's Department of Biological Sciences, has done considerable past research on the surprisingly negative roles MUC1 can play in a variety of cancers. The association of the protein with cancer is very strong -- as the article notes, "the National Cancer Institute ranked MUC1 as the second best target antigen for the development of cancer vaccines."

Mukherjee also does work on the interaction of cancer and pathogen infections. "Now it is known that about 20% of all malignancies, especially epithelial malignancies, are associated with some sort of infection, viral or bacterial, persistent inflammation being the root cause" she notes.

Mukherjee explains that a lot is now known about viruses and the biological mechanisms involved - the association of HPV with cervical cancer, for example.

"But there is very little known about what causes cancers associated with bacterial infections... not much is known about this. But when there are bacterial infections that have definitely been linked to cancer -- like H. pylori with stomach cancer and ulcers - that appears to have to do with the basic persistence of the bacteria," she said.

Persistent infections may be different because of the effects of their long-term attacks on cellular defense mechanisms.

"But if these persistent bacterial infections cause aberrations on the epithelial layers, mucins must be involved because every glandular epithelial cell has mucins and we know that mucins are the first protective layer in any bacterial infection."

Imbedded in the epithelial cell membrane, with its outside end coated with attached sugars and its inside end floating largely naked in the cell's cytoplasm, MUC1 serves a largely protective role, Mukherjee explains. Molecules on the surface of bacterial cells bind to the mucosal layer or to the glycosolated end of MUC1, but the cell is ready for the attack and responds.

"Attachment by the bacteria triggers MUC1 to shed its extracellular domain (the glycosolated section) with the bacteria attached, and the whole thing goes to the mucous layer, where the bacteria is removed," she said. "It thus works as an anti-inflammatory by pushing the attacking bacteria out and engulfing it into the sugary molecule."

However, the process can have side-effect, she explains: "That's mainly how MUC1 works, but what happens sometimes when MUC1 sheds, its remaining outside and cytoplasmic tail (the protein's inner segment) gets activated. A persistent bacterial barrage on a cell activates some cytoplasmic tail and we know that when the cytoplasmic tail is activated it can trigger signaling pathways that cause cancer."

MUC1 can thus play a dual role during infection, either being anti-inflammatory by staving off bacterial attack, or pro-inflammatory, triggering inflammation processes, which, in turn, can cause malignancy.

"The dual role of MUC1 as protective and oncogenic in the presence of microbial infection is, in a nutshell, what this article is about," she said. "There are pieces of research out there that point to this, but we are trying to pull them together."

The article surveys studies on a dozen common infections by bacteria and viruses that are known to involve MUC1 and notes a limited number of examples where the protein is known to play a pro-inflammatory role.

"The field has only looked at these mechanisms in small number of infection-associated cancers, and even fewer where bacteria are involved," she noted. "We hope our hypothesis leads to people looking at this in a more scientific manner."

Mukherjee's hypothesis stresses the central role of MUC1 and mucins in targeting future research. Because of strong connections between the protein and cancer processes in epithelial cells and the protein's strong involvement in combating microbial infections, it is an obvious, yet understudied connection between infection and cancer.

"The idea is that at some point we are going to have to start studying mucins more seriously," she said. "Rather than only studying mucins in already transformed cancer cells, we need to be studying them before the cells transform and see what is going on. The work being done on the cancer side needs to be connected with the work on the bacterial side, and the role of infection in triggering inflammation."

Adolescent binge drinking modifies gene expression in a fashion that increases susceptibility to anxiety and alcohol use disorders in adulthood, according to research in rats recently published in eNeuro. Targeting the microRNAs responsible could be a new route for undoing the damage of alcohol use caused during adolescence.

Previous researchers found that microRNA, small bits of RNA that modify how genes are expressed rather than coding for a protein, are involved in how early-life alcohol exposure changes the brain, but the exact mechanism was unknown.

Kyzar et al. exposed adolescent rats to alcohol and measured the resulting levels of miR-137, one type of microRNA, in the rats' amygdalae. The rats exposed to alcohol displayed increased levels of miR-137, resulting in lower expression of proteins necessary for healthy neuron growth and branching. In adulthood, the rats displayed higher levels of anxiety behaviors and a higher preference for alcohol compared to control rats. Inhibiting miR-137 in the amygdala reversed the anxiety and alcohol preference in the rats with an adolescent drinking history.

The drug ketamine decreases alcohol consumption in male, but not female, rats, according to new research published in eNeuro. The findings suggest that ketamine may be a viable treatment option for male patients with an alcohol use disorder.

Prior studies found that ketamine reduces alcohol use disorder symptoms in both rats and humans, but the drug was administered once, rather than over a more realistic treatment time period. Ketamine is itself an addictive drug, so it is critical to examine how it affects patients over extended use.

Strong et al. divided male and female rats into groups based on how much alcohol they were prone to consume. The rats were allowed unrestricted access to alcohol three times a week. Three weeks later, ketamine treatments began.

Ketamine administration reduced alcohol consumption in high-consumption male rats, and the effects lasted at least three weeks after the ketamine treatments ended. Ketamine did not affect the habits of high-consumption female rats and increased drinking in low-consumption females. The female rats also displayed a higher risk of abusing ketamine compared to the male rats.

Podcast permanent link: https://soundcloud.com/cmajpodcasts/190355-res

The overall rate of new cancer cases is decreasing in men but increasing in women younger than 80 years, and obesity-related cancers are increasing in young people, according to a study on cancer trends in Canada from 1971 to 2015 published in CMAJ (Canadian Medical Association). http://www.cmaj.ca/lookup/doi/10.1503/cmaj.190355.

"The most striking results from these analyses relate to increasing incidence trends among younger adults for breast, colorectal, pancreatic, endometrial and kidney cancers," writes Dr. Darren Brenner, Cumming School of Medicine, University of Calgary, with coauthors. "Obesity is a risk factor for these cancer sites, and the rising incidence runs parallel to the growing prevalence of obesity in recent decades."

The study, which included almost 5.2 million cancer cases diagnosed in Canada between 1971 and 2015, looked at cancer trends by age and birth cohort (patients grouped by year/decade of birth). Cancer incidence -- the rate of new cases -- is well documented in Canada, but less is known about trends by age groups.

"The trend among younger adults is of greater concern because they are ineligible for most cancer screening programs," write the authors.

Other key findings:

There has been an overall increase in cancers not normally occurring at younger ages, particularly breast and colorectal cancer.

The highest increase in cancer incidence is for women aged 30-39 years.

Cancer incidence has decreased in women aged 80-89 years.

The most recent trends show statistically significant decreases in the incidence of cervical, lung, bladder and prostate cancer, across most age categories.

The overall recent decrease in cancer incidence is due to declines in cancer in people older than 50 years.

The reductions in cancer incidence across age groups for several cancer types are most likely the result of primary and secondary prevention activities, including smoking cessation programs, which have decreased lung cancer, and sun safety behaviours, which have led to lower rates of melanoma in women younger than 40 and in men younger than 50 years. Endoscopy and fecal-based screening programs for colorectal cancer and screening for cervical cancer have contributed to declining rates in these cancers.

However, a rise in the use of prostate-specific antigen (PSA) testing resulted in sharp increases in prostate cancer diagnoses between 1990 and 2007, and thyroid cancer has also been over-diagnosed.

Age-specific cancer rates over time help identify the impact of changes in practice such as screening programs, better diagnosis and changing risk factors. Further efforts to reduce obesity, promote additional cancer prevention programs and further research into risk factors that may be causing cancer in younger age groups are essential.

ANN ARBOR, Mich. -- Telling the difference between a teen's normal ups and downs and something bigger is among top challenges parents face in identifying youth depression, a new national poll suggests.

Though the majority of parents say they are confident they would recognize depression in their middle or high school aged child, two thirds acknowledge barriers to spotting specific signs and symptoms, according to the C.S. Mott Children's Hospital National Poll on Children's Health at the University of Michigan.

Forty percent of parents struggle to differentiate between normal mood swings and signs of depression, while 30% say their child is good at hiding feelings.

"In many families, the preteen and teen years bring dramatic changes both in youth behavior and in the dynamic between parents and children," says poll co-director Sarah Clark. "These transitions can make it particularly challenging to get a read on children's emotional state and whether there is possible depression."

Still, a third of parents polled said nothing would interfere with their ability to recognize signs of depression in their child.

"Some parents may be overestimating their ability to recognize depression in the mood and behavior of their own child," Clark says. "An overconfident parent may fail to pick up on the subtle signals that something is amiss."

The poll also suggests that the topic of depression is all too familiar for middle and high school students. One in four parents say their child knows a peer or classmate with depression, and 1 in 10 say their child knows a peer or classmate who has died by suicide.

Indeed, rates of youth suicide continue to rise. Among people ages 10 to 24 years old, the suicide rate climbed 56% between 2007 and 2017, according to the Centers for Disease Control and Prevention.

"Our report reinforces that depression is not an abstract concept for today's teens and preteens, or their parents," Clark says.

"This level of familiarity with depression and suicide is consistent with recent statistics showing a dramatic increase in suicide among U.S. youth over the past decade. Rising rates of suicide highlight the importance of recognizing depression in youth."

Compared to the ratings of their own ability, parents polled were also less confident that their preteens or teens would recognize depression in themselves.

Clark says parents should stay vigilant on spotting any signs of potential depression in kids, which may vary from sadness and isolation to anger, irritability and acting out. Parents might also talk with their preteen or teen about identifying a "go to" adult who can be a trusted source if they are feeling blue, Clark says.

Most parents also believe schools should play a role in identifying potential depression, with seven in 10 supporting depression screening starting in middle school.

"The good news is that parents view schools as a valuable partner in recognizing youth depression," Clark says.The bad news is that too few schools have adequate resources to screen students for depression, and to offer counseling to students who need it."

Clark encourages parents to learn whether depression screening is taking place at their child's school and whether counseling is available for students who screen positive. Given the limited resources in many school districts, parents can be advocates of such efforts by talking to school administrators and school board members about the importance of offering mental health services in schools.

The nationally representative Mott Poll report is based on responses from 819 parents with at least one child in middle school, junior high, or high school.

Our expert's guide for parents on how to talk to children and teens about depression and suicide.