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Saturday, January 11, 2020

How sewage plants can remove pharmaceuticals from wastewater

A study of seven wastewater treatment plants in the Eastern United States reveals a mixed record when it comes to removing medicines such as antibiotics and antidepressants.
The research points to two treatment methods — granular activated carbon and ozonation — as being particularly promising. Each technique reduced the concentration of a number of pharmaceuticals, including certain antidepressants and antibiotics, in water by more than 95%, the scientists’ analysis found.
Activated sludge, a common treatment process that uses microorganisms to break down organic contaminants, serves an important purpose in wastewater treatment but was much less effective at destroying persistent drugs such as antidepressants and antibiotics.
The take-home message here is that we could actually remove most of the pharmaceuticals we studied. That’s the good news. If you really want clean water, there are multiple ways to do it.”
Diana Aga, PhD, Henry M. Woodburn Professor of Chemistry, University at Buffalo College of Arts and Sciences
“However, for plants that rely on activated sludge only, more advanced treatment like granular activated carbon and/or ozonation may be needed,” Aga adds. “Some cities are already doing this, but it can be expensive.”
The findings are important because any drugs discharged from treatment plants can enter the environment, where they may contribute to phenomena such as antibiotic resistance, or be consumed by wildlife.
“Our research adds to a growing body of work showing that advanced treatment methods, including ozonation and activated carbon, can be very effective at removing persistent pharmaceuticals from wastewater,” says Anne McElroy, PhD, Professor and Associate Dean for Research in the Stony Brook University School of Marine and Atmospheric Sciences.
The study — funded by New York Sea Grant — was published in November in the journal Environmental Science: Water Research & Technology.
Aga and McElroy led the project, with UB chemistry PhD student Luisa Angeles as first author. The paper was a partnership between researchers at UB, Stony Brook University, the Hampton Roads Sanitation District and Hazen and Sawyer, a national water engineering firm that designs advanced wastewater treatment systems, including some of the systems studied.
The research analyzed a variety of technologies in use at seven wastewater treatment plants in the Eastern U.S., including six full-scale plants and one large pilot-scale plant. According to the paper, “more precise locations are not provided in order to protect the identity” of the facilities.
Angeles says the study’s findings could guide future decision-making, especially in areas where water is scarce and in cities that may want to recycle wastewater, converting it into drinking water.
The research is also important for environmental conservation. It demonstrated that larval zebrafish did not change their behavior when they were exposed to wastewater discharged from treatment plants. However, much more work is needed to understand how longer-term exposures may impact wildlife, Aga says.
In a separate study in 2017, Aga’s team found high concentrations of antidepressants or the metabolized remnants of those drugs in the brains of numerous fish in the Niagara River, part of the Great Lakes region.
Scientists still don’t fully understand the behavioral and ecological impacts that may occur when chemicals from human medicines build up in wild animals over time, Aga says.
Though wastewater treatment plants were historically designed and operated for purposes such as removing organic matter and nitrogen from used water, the new research and other prior studies demonstrate that these facilities could also be harnessed to remove different classes of medicines.
Source:
Journal reference:
Angeles, L. F. et al. (2020) Assessing pharmaceutical removal and reduction in toxicity provided by advanced wastewater treatment systems. Environmental Science: Water Research & Technology. doi.org/10.1039/C9EW00559E.

US IPO Week Ahead

Chinese immunotherapy biotech I-Mab Biopharma (IMAB) plans to raise $100 million at an $876 million market cap. I-Mab would be the first Chinese biotech to IPO in the US in over two years and the second largest Chinese biotech to IPO in the US ever.
Chinese cancer diagnostics provider AnPac Bio-Medical Science (ANPC) plans to raise $22 million at a $150 million market cap.
Lock-up periods will be expiring for nine companies. On Tuesday, January 14: Fulcrum Therapeutics (FULC), Mirum Pharmaceuticals (MIRM), and Phreesia (PHR). On Wednesday, January 15: Innate Pharma (IPHA).
Street research is expected for Monopar Therapeutics (MNPR) on Monday, January 13.

Life sciences software maker Schrödinger files for a $100 million IPO

Schrödinger, which provides a software platform for life sciences and materials research, filed on Friday with the SEC to raise up to $100 million in an initial public offering.
The New York, NY-based company was founded in 1990 and booked $77 million in revenue for the 12 months ended September 30, 2019. It plans to list on the Nasdaq under the symbol SDGR. Morgan Stanley, BofA Securities, Jefferies, and BMO Capital Markets are the joint bookrunners on the deal. No pricing terms were disclosed.

Talc Powder Not Linked to Ovarian Cancer in Prospective Datasets

New research on a quarter-million women from four U.S. cohorts found no significant association between ovarian cancer and the use of powder-based products in the vaginal area.
Over a median follow-up of 11.2 years, incidence of ovarian cancer was 61 cases per 100,000 person-years among women who used powder in the genital area at any point compared with 55 cases per 100,000 for never users, a non-statistically significant difference (estimated HR 1.08, 95% CI 0.99-1.17), reported Katie O’Brien, PhD, of National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina, and colleagues.
That translated to a risk difference of just 0.09% at age 70 (95% CI -0.02% to 0.19%), the researchers estimated.
Likewise, as described in JAMAno significant difference was seen when comparing women considered frequent users (at least once a week) against never users (HR 1.09, 95% CI 0.97-1.23). Or for long-term users (at least 20 years) versus never users (HR 1.01, 95% CI 0.82-1.25).
“[T]his is, to our knowledge, the largest study of this topic to date, and it is believed that no other large prospective cohorts have collected data on powder exposure in the genital area,” O’Brien’s group wrote.
Since the 1976 ban of asbestos from cosmetic talc, the International Agency for Research on Cancer has called talc-based body powder a “possible” carcinogenic based on case-control studies and a meta-analysis that found an association between its use on or near the vagina (on underwear, sanitary napkins) and ovarian cancer.
“However, these findings may be affected by recall bias, and a recent surge in talc-related lawsuits and media coverage has increased this possibility,” O’Brien’s group wrote. “Thus, it is crucial to evaluate the talc-ovarian cancer association using prospective data.”
For their study, they pooled data from 81,869 women in the Nurses’ Health Study (enrollment 1976), 61,261 women from the Nurses’ Health Study II (enrollment 1989), 40,647 participants from the Sister Study (enrollment 2003-2009), and 73,267 participants in the Women’s Health Initiative Observational Study (enrollment 1993-1998). Median age at enrollment across the four cohorts was 57.
Ovarian cancer was diagnosed in 2,168 women across the studies, for an incidence of 58 cases per 100,000 person-years. Overall, 38% had reported using powder in the genital area, with long-term use in 10% and frequent use in 22%.
“One of the primary drivers of research on genital use of talc-based products and ovarian cancer has been the potential link between talc and asbestos, which can occur together in nature,” O’Brien’s group wrote. “In an analysis limited to the older cohorts in which women may have started using powder before the asbestos ban of 1976, the estimated effect remained consistent, with no association observed in the younger cohorts.”
Recent reports have suggested, however, that some talc-based products may have contained asbestos after this ban.
“The putative etiologic mechanism for talc as a causative agent in epithelial ovarian cancer is via uptake into the vagina, through the cervix and uterus, and through the fallopian tubes into the peritoneal cavity,” explained Dana Gossett, MD, MSCI, of University of California San Francisco, and Marcela del Carmen, MD, MPH, of Harvard University Medical School in Boston, in an accompanying editorial. “The evidence of talc in ovarian specimens lends credence to a transgenital transit mechanism.”
When the current analysis was restricted to women with patent reproductive tracts, an association between ever use of powder and ovarian cancer seemed to surface (HR 1.13, 95% CI 1.01-1.26), but tests for interaction between those with and without patent reproductive tracts lacked significance (P=0.15).
Other subgroup analyses — age, menopausal status, race, follow-up time, use of hormone therapy, body mass index, parity, hysterectomy, and tubal ligation — revealed no significant differences.
“[D]espite 3.8 million person-years of observation in the study population, the number of ovarian cancer cases was small, and it is possible that the study was underpowered to detect small increases or decreases in ovarian cancer rates,” Gossett and del Carmen wrote. “Future analyses would be strengthened by focusing on women with intact reproductive tracts, with particular attention to timing and duration of exposure to powder in the genital area.”
They pointed out that in women with patent reproductive tracts, frequent powder use appeared to increase the risk for ovarian cancer (HR 1.19, 95% CI 1.03-1.37, P=0.03 for trend), though no association was seen for long-term use.
Gossett and del Carmen cautioned that with the currently low rates (~25%) of powder use among women in the U.S., acquiring these data may not be attainable.
The study was supported by the Intramural Research Program of the National Institutes of Health; the National Institute of Environmental Health Sciences; the U.S. Department of Defense Ovarian Cancer Research Program; the National Heart, Lung, and Blood Institute; and the U.S. Department of Health and Human Services.
O’Brien reported no conflicts of interest. Co-authors disclosed relationships with Pfizer, AMAG, Mithra, Merck; and institutional support from Allergan, Myovant, and Endoceutics.
Gossett disclosed a relationship with Bayer related to the Mirena intrauterine device.

Prozac fights deadly childhood brain cancer

The anti-depressant drug Prozac could be used to tackle one of the deadliest childhood tumours and possibly other types of cancer, scientists said.
Fluoxetine—the chemical name for Prozac—works to fight the highly aggressive neuroblastoma, which is most common in young children.
The breakthrough led by Brunel University London could spare young patients treatment with highly toxic cocktails of chemotherapy drugs and radiation.
“Prozac has the potential to be used in children with neuroblastoma as a new and effective anti- drug, but with less toxicity than current cancer treatments,” said Professor Arturo Sala.
Publishing the results today in Oncogenesis, the team show Prozac can stabilise a protein encoded by the gene CDKN1B that kills neuroblastoma cells and slows their growth. And crucially, the doses needed are safe for children, which they call ‘a major clinical advance’.
Researchers found significantly fewer metastases (when cancer spreads from one part of the body to another) in organs such as liver, kidneys and bone marrows in mice on Prozac.
The idea to use Prozac to treat cancer came after previous studies found people on long-term treatment for psychotic illnesses have lower cancer rates.
Working with Italy’s D’Annunzio University of Chieti–Pescara, they made the discovery using a gene-editing tool called CRISPR. CRISPR let them target the CDKN1B gene, which is downregulated in cancers with mutation of the oncogene MYC, such as .
Prozac could potentially treat other cancers too, said Prof Sala: “Since Prozac targets MYC-expressing cancer cells, it could possibly be used to treat a wide range of human cancers with high MYC expression, for example big killers such as  or prostate cancer.”
Neuroblastoma is the most commonly diagnosed cancer in the first year of life and is responsible for most cancer deaths in babies. Even with surgery, radiotherapy and chemotherapy, the average patient with high-risk metastatic disease lives less than 3 years. Relapse is common, so finding a less toxic drug to prolong remission could be life-changing.
The results, Prof Sala said, “warrant the opening of clinical trials in which long-term Prozac treatments could be included in consolidation or post-consolidation therapies in patients who are at high risk of disease relapse”.

Explore further

More information: Sandra Bibbo’ et al. Repurposing a psychoactive drug for children with cancer: p27Kip1-dependent inhibition of metastatic neuroblastomas by Prozac, Oncogenesis (2020). DOI: 10.1038/s41389-019-0186-3

Wonder drug? Metformin, diabetes med with Medieval roots

At only pennies per dose, metformin is a Type 2 diabetes drug with distant roots in Medieval folk medicine and a powerful capacity to reduce body weight, fat mass, circulating glucose—and prevent the disorder altogether in people at elevated risk.
New research on the most widely prescribed Type 2  in the world arrives as a global obesity epidemic continues unabated. Obesity is the leading risk factor for Type 2 diabetes, a metabolic disorder.
While scientists have found that more than 60 percent of ‘s ability to control Type 2 is derived from lowering , it has taken until now to tease out key molecular mechanisms underlying how the medication does its job.
In the United Kingdom, Dr. Stephen O’Rahilly and colleagues at the University of Cambridge, are in the vanguard of scientists worldwide who have tackled a series of metformin studies in humans and laboratory animals. The team has shown how the  causes , even among  who don’t have diabetes.
Outside of their work, other scientists are hailing metformin as a wonder drug not only because of its effect on Type 2 diabetes, but because of its emerging prominence in cancer research and potential influence in the lungs of those diagnosed with tuberculosis.
“Metformin was first used as a glucose-lowering drug in patients with Type 2 diabetes,” O’Rahilly, a professor of clinical biochemistry and medicine, told Medical Xpress. “In these [patients], the weight loss can be quite modest, probably because when you reduce glucose in Type 2 diabetes, you stop calories being lost in the urine as sugar, and that works against the weight-reducing effects.
“It was only when long-term studies in non-diabetic participants were undertaken that it became clear that people who actually had good compliance with metformin lost on average around 6 percent of their body weight and could keep it off for years,” added O’Rahilly, director of the Wellcome Trust-MRC Institute of Metabolic Science-Metabolic Research Laboratories.
Reporting in the journal Nature, O’Rahilly and his team explained the relationship between metformin and a key circulating protein, a molecule known as GDF15. The initials stand for growth and differentiation factor 15. The protein is a member of the TGF-β superfamily, a vast group of cell regulatory proteins.
GDF15 carries out a wide range of biological activities and is found in a variety of tissues, regulating apoptosis and cell repair. As it turns out, GDF15 plays a potent role in the presence of metformin toward controlling Type 2 diabetes.
The mutual relationship now has been fully elucidated by O’Rahilly and his team, and for the first time, posits the molecular mechanisms underlying the weight loss that occurs among patients on the drug. Metformin works with GDF15 and by itself to induce weight loss and maintain energy balance, the team found.
“Our data does suggest that most, if not all, of the weight loss effects of the metformin require GDF15. However, metformin continues to have some effects in lowering glucose and insulin that are independent of weight loss and independent of GDF15,” O’Rahilly said.
The researchers found that “metformin treatment increases the levels [of GDF15] quite markedly in all people who take the drug regularly,” O’Rahilly said.
He described metformin as the most widely prescribed diabetes medication on the planet. Known generically as metformin, the drug is sold under the brand name Glucophage. Sixty tablets cost about $4 at prescription drug discounters, such as Walmart, in the United States.
Approved by the U.S. Food and Drug Administration in 1995, metformin had been widely prescribed for decades in Europe before it was finally given a green light in a country with more than 30 million Type 2 diabetics. The U.S. additionally has 84.1 million people with pre-diabetes, a condition that can lead to the full-blown disease.
Among medications, metformin has a long and storied past. The compound destined to become metformin was first isolated during the Middle Ages from the French lilac, a plant scientifically known as Galega officinalis. Ground flowers and leaves were administered by healers to patients suffering from constant urination, a hallmark of a disorder that later would become known as diabetes. The  in French lilac, a plant also called goat’s rue, was identified hundreds of years later as galegine, which triggered a striking reduction in blood glucose.
By the 1950s, scientists were able to exploit folk medicine uses and develop the drug that became metformin. In recent years, in vitro studies by Dr. Lloyd Trotman at Cold Spring Harbor Laboratory in New York have shown metformin to be effective against prostate cancer cells. And in November, scientists in Mexico found that metformin promotes the destruction of Mycobacterium tuberculosis bacteria in the lungs. The drug enhances the activity of antimicrobial peptides known as β-defensins. The peptides are common in lung epithelial tissue and are active against Gram negative and Gram positive bacteria.
O’Rahilly and colleagues, meanwhile, have described the benefits of metformin in both human clinical trials and experiments involving animal models. In both types of investigations, metformin influenced weight loss and GDF15 activity.
For example, in one of the human clinical trials cited in the Nature paper, the team measured circulating GDF15 and found that after two weeks on metformin, there was approximately a 2.5-fold increase in circulating GDF15. To determine if the increase was sustained, protein levels were measured six, 12 and 18 months. Patients who took metformin wound up losing about 3.5 percent of their body weight. In another trial, patients lost even more.
In wild-type mice, oral metformin also increased circulating GDF15. Protein levels additionally rose in the distal intestine and kidneys. Metformin prevented weight gain in response to a high-fat diet in the animals but not in mice lacking GDF15 or its receptor protein, GFRAL. Metformin had effects on both energy intake and energy expenditure that required GDF15, the team found.
O’Rahilly said the research has been reproduced by other teams assuring him and his colleagues that they have demonstrated how metformin lowers body weight.
“The key findings of our work have already been independently replicated by Greg Steinberg at McMaster University. We are indeed undertaking further studies to explore exactly where the GDF15 is coming from and how it is regulated,” O’Rahilly said.

Explore further

More information: Anthony P. Coll et al. GDF15 mediates the effects of metformin on body weight and energy balance, Nature (2019). DOI: 10.1038/s41586-019-1911-y

Rates charged by hospitals have soared, study finds

The rates hospitals charge for care, including inpatient, outpatient and emergency services, have skyrocketed, according to a new study published in Health Affairs.
Authored by Thomas Selden, PhD, a director of research at the Agency for Healthcare Research and Quality, the analysis looked at data from the Medical Expenditure Panel Survey to determine the differences between public and private hospital payment rates, as well as hospital charges.
The analysis found dramatic growth in hospital charges, which rose from three to five times Medicare payment rates by 2016.
For example, emergency department charges rose to about 555 percent of Medicare payment rates in 2016, up from about 225 percent of Medicare payment rates in 1996. Inpatient charges rose from about 175 percent of the Medicare payment rates in 1996, to about 350 percent. Outpatient charges also grew during the time period, from about 225 percent of Medicare payment rates to nearly 375 percent, according to the study.
The same study also found that the gap between what private and government insurers pay hospitals widened between 2000 and 2012. However, that gap narrowed between 2012 and 2016.
Access the full study here.