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SharecloseShare pageCopy linkAbout sharingImage source, Dr John WilkinsonPollution of the world’s rivers from medicines and pharmaceutical products poses a “threat to environmental and global health”, a report says.Paracetamol, nicotine, caffeine and epilepsy and diabetes drugs were widely detected in a University of York study. The research is among the most extensive undertaken on a global scale.Rivers in Pakistan, Bolivia and Ethiopia were among the most polluted. Rivers in Iceland, Norway and the Amazon rainforest fared the best. Plastic from take-out food is polluting the oceansHow clean are the UK’s rivers and lakes?Group gets funding for river pollution researchThe impact of many of the most common pharmaceutical compounds in rivers is still largely unknown.But it is already well established that dissolved human contraceptives can impact the development and reproduction of fish, and scientists fear the increased presence of antibiotics in rivers could limit their effectiveness as medicines.Image source, Dr John WilkinsonThe study sampled water from more than 1,000 test sites in more than 100 countries. Overall, more than a quarter of the 258 rivers sampled had what are known as “active pharmaceutical ingredients” present at a level deemed unsafe for aquatic organisms. “Typically, what happens is, we take these chemicals, they have some desired effects on us and then they leave our bodies,” Dr John Wilkinson, who led the research, told BBC News.”What we know now is that even the most modern efficient wastewater treatment plants aren’t completely capable of degrading these compounds before they end up in rivers or lakes.”The two most frequently detected pharmaceuticals were carbamazepine, which is used to treat epilepsy and nerve pain, and metformin, used to treat diabetes.High concentrations were also found of so-called “lifestyle consumables” like caffeine (coffee) and nicotine (cigarettes) as well as the painkiller paracetamol. In Africa, artemisinin, which is used in anti-malarial medicine, was also found in high concentrations.”We can say [the impact of the presence of such pharmaceuticals in rivers] is likely to be negative but you have to do individual tests with each one and there are relatively few studies,” Dr Veronica Edmonds-Brown, an aquatic ecologist from the UK’s University of Hertfordshire told BBC News. “This is only going to get worse as we are increasingly using pharmacological solutions to any illness whether physical or mental.”The report says the increased presence of antibiotics in rivers could also lead to the development of resistant bacteria, damaging the effectiveness of medicines and ultimately posing “a global threat to environmental and global health”. The most polluted sites were largely in low- to middle-income countries, and in areas where there was sewage dumping, poor wastewater management and pharmaceutical manufacturing. Image source, Dr John Wilkinson”We have seen contaminated rivers in Nigeria and in South Africa with very high concentrations of pharmaceuticals and this is basically down to the lack of infrastructure in wastewater treatment,” said Dr Mohamed Abdallah, Associate Professor of Emerging Contaminants at the UK’s Birmingham University. “This is most concerning because you have the most vulnerable populations with the least access to healthcare exposed to this.”On the question of what can be done, the lead author of the report, Dr Wilkinson, has a somewhat depressing outlook. “It’s going to take many people who are a lot smarter than me to tackle the problem,” he said. “One of the few things that could have an effect right now is the proper use of medicines.”That would mean making it harder to get hold of medicines like antibiotics, and tighter restrictions on doses. The full report has been published in the Proceedings of the National Academy of Sciences journal.

A new study led by researchers at Yale Cancer Center and the University of Maryland Comprehensive Cancer Center shows ixabepilone plus bevacizumab (IXA+BEV) is a well-tolerated, effective combination for treatment of platinum/taxane-resistant ovarian cancer compared to ixabepilone (IXA) alone. The data shows it also may significantly extend both progression free survival and overall survival. The results were published in the British Journal of Cancer.
“Novel approaches for relapsed ovarian cancer are desperately needed as limited effective combinations currently exist to treat our patients. The results of this study demonstrated a drug combination that may be an effective treatment for this type of ovarian cancer,” said Alessandro Santin, MD, Professor of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine and Disease Aligned Research Team Leader for the Gynecological Cancers Program at Yale Cancer Center and Smilow Cancer Hospital and senior author of the study.
Ovarian cancer is the most lethal gynecologic malignancy. According to the American Cancer Society, nearly 20,000 women will be diagnosed with ovarian cancer in the United States every year, and more than 12,000 women will die from the disease. IXA is a microtubule-stabilizing agent that may be beneficial in patients treated with platinum/paclitaxel. Bevacizumab (BEV) is an antibody that keeps new blood vessels from forming and has shown clinical activity in ovarian cancer.
In this phase II study, researchers randomly assigned 78 patients to receive IXA+BEV or IXA alone. The primary endpoint was progression-free survival (PFS), Overall survival (OS), safety, and response rates served as secondary endpoints. Researchers also examined whether the presence of the protein TUBB3 within the tumor could predict clinical response to these drugs. Among 76 evaluable patients who received IXA+BEV compared to IXA, the response rate was 33% versus 8%, with clinical benefit durable at 6 months in 37% and 3%. The addition of BEV significantly improved both PFS (5.5 months vs 2.2 months) and OS (10 months vs 6 months). Both regimens were well-tolerated.
“We expect our findings to have major implications in the field of gynecologic oncology since they add a new, effective treatment for these extremely challenging tumors for which there are otherwise few options,” said first author Dana M. Roque, MD, Associate Professor of the Division of Gynecologic Oncology at the University of Maryland School of Medicine and member of the Marlene & Stewart Greenebaum Comprehensive Cancer Center.
Other Yale authors of the study include: Gloria Huang, MD, Gulden Menderes, MD, and Elena Ratner, MD, Natalia Buza, MD, Stefania Bellone, PhD, Vaagn Andikyan, MD, Mitchell Clark, MD, Masoud Azodi, MD, Peter E. Schwartz, MD, Pei Hui, MD, PhD,Joan R. Tymon-Rosario, Justin Harold, MD, Dennis Mauricio, Burak Zeybek, and Gary Altwerger, MD.
Funding for the study was provided by RPharm-US, grants from the National Institutes of Health, the National Cancer Institute, the Deborah Bunn Alley Ovarian Cancer Research Foundation, the Discovery to Cure Foundation, the Stand Up to Cancer Foundation (SU2C), the Guido Berlucchi Foundation, and the Domenic Cicchetti Foundation.
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Materials provided by Yale University. Note: Content may be edited for style and length.

A study by researchers at Mayo Clinic Cancer Center in Florida is validating the use of genomic sequencing to predict the likelihood that patients with gastric cancer will derive benefit from chemotherapy or from immunotherapy. The study is published in Nature Communications.
“Gastric cancer is among the leading causes of cancer-related death, worldwide,” says Tae Hyun Hwang, Ph.D., the Florida Department of Health cancer chair at Mayo Clinic Cancer Center in Florida.
Dr. Hwang says most patients with gastric cancer are treated with chemotherapy, and sometimes immunotherapy, as part of their treatment plan. However, not all patients derive benefit from these therapies.
“We sought to use genomic sequencing to build a model that predicts the likelihood that a patient will derive benefit from chemotherapy or from immunotherapy,” says Dr. Hwang.
To build this model, Dr. Hwang and his team developed and implemented a machine learning algorithm that integrated genetic data from more than 5,000 patients. Then the team developed a molecular signature consisting of 32 genes that could be used to guide patient care decisions.
“We were pleased that our 32-gene signature provided not only prognostic information, but also predicted patient benefit from chemotherapy and immunotherapy,” says Dr. Hwang. “In particular, we were surprised that the 32-gene signature we identified was able to predict a patient’s response to immunotherapy because identifying reliable biomarkers for immunotherapy response in patients with gastric cancer has been a challenge for the field.”
Dr. Hwang says the 32-gene molecular signature still needs prospective validation, but he believes it eventually will be able to identify patients who are likely to respond to chemotherapy and immunotherapy. “Similarly, we would also be able to identify patients who are unlikely to benefit from chemotherapy and immunotherapy, thereby sparing them the potential side effects of these therapies,” says Dr. Hwang.
Dr. Hwang and his team also are working to develop new assays based on the expression level of a single — or several — genes to make biomarkers more accessible and easily deployed in the clinical setting. “We are working on artificial intelligence algorithms that utilize diagnostic histopathology images to identify patients most likely to derive benefit from immunotherapy,” says Dr. Hwang. “We are also studying the molecular mechanisms of immunotherapy resistance made available by the machine learning and artificial intelligence approaches that we have developed in our lab.”
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Materials provided by Mayo Clinic. Original written by Joe Dangor. Note: Content may be edited for style and length.

Scientists from Rochester Institute of Technology and Cornell University have teamed up to explore cartilage tissue’s unique properties with the hopes of improving osteoarthritis diagnosis and treatment. The team published a new paper in Science Advances outlining their findings.
Cartilage tissue in our knee and elbow joints is just a few millimeters thick but can bear loads up to 10 times the body’s weight and withstand a few hundred thousand loading cycles with minimal damage over a person’s lifespan. But the tissue does not regenerate once people reach adulthood, and damage to cartilage can be a precursor to diseases like osteoarthritis. RIT’s biophysics modelers and Cornell’s experimentalists examined what mechanically happens to cartilage tissue at the microscopic level in response to shear to help drive advances in medical imaging.
“The goal was to find a mechanistic biophysics framework that can make realistic predictions about what kind of changes are taking place in cartilage mechanics and function during various disease pathways,” said Moumita Das, co-senior author of the paper and an associate professor in RIT’s School of Physics and Astronomy. “This mathematical model is informed by experimental data, so we can combine it with noninvasive measurements like MRIs. With a map of properties for healthy and damaged cartilage tissue, doctors can make predictions about when surgical intervention is necessary just from imaging without having to do invasive procedures.”
RIT Postdoctoral Research Associate Jonathan Michel served as co-lead author on the paper, and Pancy Lwin, a mathematical modeling Ph.D. student from Myanmar, also served as a co-author. Cornell’s contributions were directed by Professor Professor Itai Cohen and Professor Lawrence Bonassar.
The paper builds on another recent study the RIT-Cornell team published in Soft Matter that looks at how cartilage’s properties resist fracture and how we can tune artificial materials to mimic those properties.
“As far as humanmade synthetic materials, nothing anyone has come up with to date can compare to cartilage,” said Das. “If we can understand the origins of cartilage’s robust and resilient properties, it can help us engineer tissues to replace cartilage or make other materials for applications such as soft robotics.”
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Materials provided by Rochester Institute of Technology. Original written by Luke Auburn. Note: Content may be edited for style and length.

Transportation is responsible for a larger share of greenhouse gas emissions than any other sector of the U.S. economy, making biofuels a promising strategy to mitigate human-driven climate change. The U.S. Renewable Fuel Standard, created by 2007 legislation, mandates that such fuels partially replace petroleum-based ones. So far, however, the mandate has been nearly entirely fulfilled by corn ethanol, a fuel that may be worse for the climate than the gasoline it replaces.
Fifteen years on, research led by the University of Wisconsin-Madison assessed the environmental impacts of corn ethanol and the policy that governs it, using a combination of econometric analyses, land use data and biophysical modeling.
The analysis, published this week in the Proceedings of the National Academy of Sciences, shows that the carbon emissions from using land to grow corn can negate or even reverse any climate advantages of corn ethanol relative to gasoline.
The results confirm what many scientists already realized: From a climate and environmental standpoint, corn ethanol is not a good biofuel solution. Instead, the findings align with the movement in bioenergy research toward developing next-generation biofuels, such as those made from perennial, non-food plants grown on land less suited for conventional agriculture.
“It basically reaffirms what many suspected, that corn ethanol is not a climate-friendly fuel and we need to accelerate the shift toward better renewable fuels, as well as make improvements in efficiency and electrification,” says lead study author Tyler Lark, a scientist in the Great Lakes Bioenergy Research Center and the Nelson Institute for Environmental Studies at UW-Madison.
The results are especially timely, he says, because the Renewable Fuel Standard mandates specific annual biofuel volumes through 2022; once these requirements expire, the Environmental Protection Agency will take over the role of determining how much and which types of biofuel should be produced each year to meet the standard. What comes next policy-wise could have a very large effect on climate change, Lark says. “It’s a pivotal moment for deciding what this policy — and our landscape — should look like moving forward.”
In their studies of changing patterns of land use in the U.S., Lark and his colleague Holly Gibbs, a UW-Madison professor of environmental studies and geography, have noted the expansion of agricultural land dedicated to commodity crops, especially corn. They suspected ethanol production might be playing a role. “We knew it was likely contributing, but we didn’t know to what extent,” Gibbs says.

A new study looking at the presence of pharmaceuticals in the world’s rivers found concentrations at potentially toxic levels in more than a quarter of the locations studied.
The new study looked at 258 rivers across the globe, including the Thames in London and the Amazon in Brazil, to measure the presence of 61 pharmaceuticals, such as carbamazepine, metformin and caffeine.
The researchers studied rivers in over half of the world’s countries — with rivers in 36 of these countries having never previously been monitored for pharmaceuticals.
The study forms part of the University of York-led Global Monitoring of Pharmaceuticals Project, which has expanded significantly over the last two years, with the new study becoming the first truly global-scale investigation of medicinal contamination in the environment.
With their latest study, the researchers found that: pharmaceutical pollution is contaminating water on every continent strong correlations between the socioeconomic status of a country and higher pollution of pharmaceuticals in its rivers (with lower-middle income nations the most polluted) high levels of pharmaceutical pollution was most positively associated with regions of high median age as well as high local unemployment and poverty rates the most polluted countries and regions of the world are the ones that have been researched the least (namely sub-saharan Africa, South America and parts of southern Asia). the activities most associated with the highest levels of pharmaceutical pollution included rubbish dumping along river banks, inadequate wastewater infrastructure and pharmaceutical manufacturing, and the dumping of the contents of residual septic tanks into rivers.The study revealed that a quarter of the sites contained contaminants (such as sulfamethoxazole, propranolol, ciprofloxacin and loratadine) at potentially harmful concentrations.

In image compression, a large file that could be cumbersome to store or share loses a small amount of visual information. This “lossiness” largely preserves the image while vastly reducing its file size — and serves as the inspiration for a new research direction in genomics, according to Justin Pritchard, assistant professor of biomedical engineering.
Pritchard and a Penn State-led team of interdisciplinary researchers developed a methodology for “compressing” extensive genetic data libraries to more manageable sizes. They published their findings in Nature Communications on Feb. 2.
“This idea of compression dramatically reduces the scale of the experiments, opening up possibilities for new experiments,” said Pritchard, who also holds the Dorothy Foehr Huck and J. Lloyd Huck Early Career Entrepreneurial Professorship. “This can unlock biological mysteries, such as why different genes and drugs work differently together, and it allows us to unravel very complicated biology using simpler experiments.”
The researchers referred to genome-scale CRISPR experiments containing data on thousands of gene effects tested in different human cell types. The effect when the gene is turned off can vary between cell types, so a large number of cells is often needed to understand the interplay between genes and phenotypes.
To predict the larger genome-scale effects from the smaller “compressed” CRISPR library, the team used a custom algorithm rooted in a common machine learning technique known as random forests. This method incorporates data provided by the researchers into a series of randomly generated decision trees that collectively produce predictions about the relationship between gene inactivation and cell growth. The model was trained on the majority of the data — leaving one data subset out — and then initially validated by testing its capacity to predict data for the omitted subset. This accuracy extended to datasets that were generated in different labs using different experimental conditions and CRISPR libraries.
This performance was possible using only a small percentage — about 1% — of the original library’s information. Finally, the Penn State group performed new experiments in which they physically built these “lossy compression libraries” using synthetic biology techniques and validated the predictions in new experiments.
“A genome-scale experiment probes 18,000 genes,” Pritchard said. “Using machine learning, we tunably compressed the scale of the experiment to as few as 200 genes. Despite the loss of some data in the compression, we found that a subset of 200 genes could provide surprisingly good information on the full 18,000 genes.”
The technique also opens opportunities for other research, according to Pritchard. It showed transferability, meaning it could make accurate predictions matching information from entirely different datasets despite only being trained on the CRISPR data. The capacity to reduce the number of genes also enables more research on cells that can be difficult or impossible to aggregate in large amounts, such as cells within a living organism.
“We’re excited about the future of this research,” Pritchard said. “We can alter the composition of these lossy compression sets in real time, for different experimental questions and conditions in areas from cancer biology to biopharmaceuticals, using newer machine learning techniques. The method also helps us improve basic science by answering questions about how the genome works and encodes information on cell growth.”
Boyang Zhao, Edward P. O’Brien, Luke Gilbert, Scott Leighow and Yiyun Rao from Penn State contributed to this work. Zhao contributed as first author and is also affiliated with Quantalarity Research Group in Houston. Gilbert is affiliated with the University of California San Francisco and the Helen Diller Family Comprehensive Cancer Center in San Francisco.
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Materials provided by Penn State. Original written by Gabrielle Stewart. Note: Content may be edited for style and length.

This Valentine’s Day, a new Northwestern Medicine study shines a spotlight on an important but often overlooked matter of the heart — optimizing one’s cardiovascular health before getting pregnant.
More than one in two young women between the ages of 20 and 44 who gave birth in the United States in 2019 had poor heart health before becoming pregnant, the study found. Poor heart health puts expectant mothers and their babies at risk, with heart disease causing more than one in four pregnancy-related deaths.
“As women, we tend to think about the baby’s health once we become pregnant, but what so many women don’t realize is the very first thing they can do to protect their babies (and themselves) is to get their heart in shape before they even conceive,” said senior study author Dr. Sadiya Khan, assistant professor of medicine in cardiology and epidemiology at Northwestern University Feinberg School of Medicine and a Northwestern Medicine physician.
The study will be published Feb. 14 in Circulation, the American Heart Association’s (AHA) peer-reviewed flagship journal, as part of a themed issue for the Go Red for Women Campaign that was developed by the AHA in 2004 to highlight awareness about heart disease risks in women.
More than half the women in the study had at least one risk factor for poor heart health, including overweight/obesity, hypertension or diabetes before becoming pregnant. Being overweight or obese was the most common reason for poor heart health before pregnancy, the study found.
“Women with favorable heart health before pregnancy are less likely to experience complications of pregnancy and are more likely to deliver a healthy baby,” said lead study author Dr. Natalie Cameron, an internal medicine specialist and instructor at Feinberg and a Northwestern Medicine physician. “Even more importantly, optimizing heart health before and during pregnancy can prevent the development of heart disease years later. Clinicians can play a key role in both assessing and optimizing heart health prior to pregnancy.”
Better heart health before pregnancy in the West, Northeast

Findings by researchers from Germany support the view that hyperactive immune cells in the brain can have a protective effect in the course of neurodegenerative diseases. Experts from Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Ludwig-Maximilians-Universität München (LMU) and LMU Klinikum München report on this in the scientific magazine The EMBO Journal. The scientists are currently considering that modulating the activity of immune cells in the brain via a receptor called TREM2 may significantly impact neurodegenerative disease processes. Thus, they see activating TREM2 as a promising approach for drug research.
The immune cells of the brain — called “microglia” — act against pathogens, help to clear up cellular debris and also maintain neuronal health. However, in Alzheimer’s disease and other neurodegenerative diseases, these cells enter a “hyperactive” state, traditionally considered an excessive immune response because it is associated with chronic and thus harmful inflammatory processes. However, the current results put this view partly into a new perspective. “Contrary to common belief, our findings support the hypothesis that hyperactive microglia have their good side. Recently, there has already been some evidence for this. Our study now provides further indications,” says Christian Haass, a research group leader at DZNE and professor of biochemistry at LMU München.
Antibodies in Action
In previous studies, Haass and colleagues had identified a protein called TREM2, which is anchored in the cell membrane of microglia, as an “activity switch.” Using antibodies that bind and activate TREM2 — co-developed with the U.S. company Denali Therapeutics — the researchers succeeded in toggling this molecular switch, thereby boosting microglial activity. “At the time, we saw in laboratory experiments that microglia activated in this way more effectively eliminate the protein deposits typical of Alzheimer’s disease, the notorious amyloid plaques,” explains Haass. “However, we were concerned that too much activation of microglia could cause harm, as is commonly believed.”
The current studies expand upon the investigations carried out back then. Instead of increasing microglia activity, the researchers now pursued the opposite. “We wanted to know the impact on disease pathology when we downregulated the activity of hyperactive microglia,” Haass says. This time, an antibody was used that disabled the TREM2 receptor and thus reduced the activity of the immune cells in the brain.
Laboratory Studies
As an example of a neurodegenerative disease, the researchers focused on “GRN-associated frontotemporal lobar degeneration,” GRN-FTLD for short. “This is a genetic, rare form of dementia that comes with a wide range of abnormal behaviors. Some of the affected individuals are impulsive and aggressive, while others are apathetic,” explains Prof. Dominik Paquet, a neurobiologist at the Institute for Stroke and Dementia Research at LMU Klinikum München, whose research group was also involved in the current study.
“GRN-FTLD is well-described and there are good options for laboratory studies. Therefore, we used this disease as an example to investigate how hyperactive microglia contribute to the pathology of neurodegeneration,” says Dr. Anja Capell, biochemist at LMU München, who co-designed the current study.
The research team used different cell cultures for their experiments. These included either microglia derived from human stem cells or cells obtained directly from patients with GRN-FTLD. Mice with genetic traits characteristic of GRN-FTLD were also studied.
Less Microglial Activity Didn’t Make It Better
“Our data suggest that it is indeed possible to diminish microglia activation state via inhibition of TREM2 signaling. Hyperactivity is therefore reversible and not a one-way street, which is not a given,” says Anja Capell. “However, the pathology was not improved but worsened as a result; loss of contacts between neurons, the synapses, increased. We also found that the level of a biomarker for neuronal damage rose.”
These results are unexpected. “We were surprised ourselves. But contrary to common belief, hyperactivated microglia seem to retain certain neuroprotective functions. At least this applies to the model system we studied,” says Christian Haass. “Conversely, this means that a controlled increase in the activity of microglia could help to contain the disease process to some extent. For this, I consider targeting the TREM2 receptor with an agonist antibody, that’s an activating antibody, to be promising. We intend to pursue this idea further.”

While the word “mutation” may conjure up alarming notions, a mutation in brain immune cells serves a positive role in protecting people against Alzheimer’s disease. Now University of California, Irvine biologists have discovered the mechanisms behind this crucial process. Their paper appears in the journal Alzheimer’s and Dementia.
The investigation centered on a variant of the PLCG2 gene, which makes the instructions for producing an enzyme important to brain immune cells called microglia. “Recently the mutation, which is known as P522R, was shown to lower the risk of developing late-onset Alzheimer’s,” said Hayk Davtyan, Ph.D., senior researcher in the laboratory of Mathew Blurton-Jones, professor of neurobiology & behavior, where the study was conducted. The project was led by assistant project scientist Christel Claes, Ph.D., the paper’s first author.
The scientists used CRISPR gene-editing technology to generate the protective mutation in human stem cells and then implanted microglia derived from those stem cells into humanized rodent models of Alzheimer’s disease.
“Our research showed for the first time that the P522R variant increased expression levels of several microglial genes that are reduced in people with Alzheimer’s. This provides some of the first evidence to explain how this protective mutation might reduce Alzheimer’s risk,” Davtyan said.
The variant also increased the number of T-cells, or white blood immune system cells, in the brain suggesting that it may increase the activation of other important aspects of immune function.
The results will help in designing further studies to understand exactly how microglia and T-cells interact to slow Alzheimer’s progression.
“Beyond that, the next step could be to identify drugs that can safely increase the activity of the PLCG2 enzyme and further promote protective microglial functions,” he said.
First author Christel Claes wonders whether a TREM2 stimulating antibody, like the one currently in a Phase 2 clinical study from Alector (AL002), could exert similar protection in AD patients as the P522R variant.
“It is well known that the PLCG2 P522R mutation increases TREM2 downstream signaling, an AD risk variant, thus it will be very interesting to study the effect of TREM2 stimulating antibodies on microglia-T cell crosstalk. Studies like ours pave the way to find new strategies to treat or prevent this disease that is taking such a toll on humanity, this is what drives us as neuroscientists.” said Davtyan.
The project was supported by a BrightFocus Postdoctoral Fellowship, the Cure Alzheimer’s Fund, National Institutes of Health and National Institute on Aging.
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Materials provided by University of California – Irvine. Note: Content may be edited for style and length.