Infertility is a growing problem and the number of in vitro fertilisation procedures is increasing rapidly. It is already known that women who become pregnant by assisted reproduction techniques have an increased risk of preeclampsia, repeated miscarriages and the baby being born prematurely and with a lower birth weight. Yet, the reasons behind this have not been fully understood.

“Before a planned in vitro fertilisation, the man’s sperm sample is analysed for concentration, motility and morphology. But there are men who, according to this analysis, have normal sperm, but still have reduced fertility,” says Amelie Stenqvist, lecturer at Lund University. She received her PhD from Lund and now works as a specialist in gynaecology and obstetrics at Skåne University Hospital in Malmö.

Around 20-30 per cent of babies born through in vitro fertilisation have fathers with damaged DNA in their sperm, as shown by elevated levels of DNA fragmentation. The DNA fragmentation index (DFI) is a measure of the amount of strand breaks in the DNA and is used to provide important new information about male fertility. Sperm with DNA damage may still be fertile, but the chances of fertilisation are lower and if the percentage of DFI exceeds 30 per cent, the chances of natural conception are close to zero.

Although current in vitro techniques mean that men with a high DFI can become fathers, until now very little has been known about the impact of DNA fragmentation on pregnancy and the health of the baby. It has been difficult to research the topic because the DFI value is not included in the standard measurements currently taken by Sweden’s fertility clinics. It also requires a large study population and access to national medical registries.

“Since half of the placenta’s DNA comes from the father and placental development and function play a central role in preeclampsia, we wanted to investigate whether a high percentage of DNA damage in the sperm affected the risk of preeclampsia,” says Aleksander Giwercman.

He is a professor of reproductive medicine at Lund University, a consultant at Skåne University Hospital in Malmö and one of the researchers behind ReproUnion**. Aleksander Giwercman also led a research study that included 1,660 children conceived through IVF and ICSI at the Reproductive Medicine Centre in Malmö over the period 2007-2018*.

The results showed that in the 841 couples who underwent IVF, a DFI of over 20 per cent doubled the risk of the woman developing preeclampsia (10.5 per cent) and also increased the risk of premature birth. In the IVF group with a DFI below 20 per cent, there was a 4.8 per cent risk of preeclampsia, which is comparable to pregnancies that occur naturally. For couples undergoing ICSI, there was no association with preeclampsia.

“Today, DFI analysis is only performed at some fertility clinics in Sweden, but we think that it should be introduced as standard at all clinics. It can give couples answers as to why they are not getting pregnant and can influence the chosen method of assisted fertilisation. Not only that, our latest results show that a DFI analysis could be used to identify high-risk pregnancies,” says Aleksander Giwercman.

What makes this finding even more interesting is that high DNA fragmentation in sperm is linked to the overall health of the father and is potentially treatable. Most DNA damage is caused by oxidative stress, which is an imbalance between harmful molecules and the antioxidants that protect cells. Other factors that increase DNA fragmentation include the man’s age, smoking, obesity and infections.

“The next step is to identify which group of men respond best to methods to prevent and treat sperm DNA damage, and to test these methods to prevent pregnancy complications,” concludes Amelie Stenqvist.

They can power heavy-duty trucks and buses and are suited for off-road and agricultural equipment and backup power generators, providing cleaner alternatives to diesel engines.

Yet they are not entirely clean. They emit nitrogen oxides during the high-temperature combustion process. Nitrogen oxides react with other compounds in the atmosphere to form harmful ozone and fine particulate matter, which aggravate our lungs and lead to long-term health problems.

Fortunately, UC Riverside scientists have discovered a low-cost method to significantly reduce this pollution from hydrogen engines by improving the efficiency of their catalytic converters.

As reported in the journal Nature Communications, the researchers found that infusing platinum in catalytic converters with a highly porous material called Y zeolites greatly enhances the reactions between nitrogen oxides and hydrogen, converting them into harmless nitrogen gas and water vapor.

Compared to a catalytic converter without zeolites, the amount of nitrogen oxides converted to harmless substances increased by four to five times at an engine temperature of 250 degrees Celsius, the study found. The system was particularly effective at lower temperatures, which is crucial for reducing pollution when engines first start up and are still relatively cool.

What’s more, the technology can also reduce pollution from diesel engines equipped with hydrogen injection systems, explained Fudong Liu, the corresponding author and associate professor of chemical and environmental engineering at UCR’s Bourns College of Engineering. The hydrogen injection would be similar to the injection systems used in selective catalytic reduction systems for big-rig diesel trucks.

Zeolites are low-cost materials with a well-defined crystalline structure composed primarily of silicon, aluminum, and oxygen atoms. Their large surface area and three-dimensional, cage-like framework of uniform pores and channels allow for more efficient breakdown of pollutants.

By physically mixing platinum with Y zeolite — a synthetic type from the broader family of zeolite compounds — the researchers created a system that effectively captures water generated during the hydrogen combustion process. This water-rich environment promotes hydrogen activation, which is key to improving nitrogen reduction efficiency.

Shaohua Xie, a research scientist at UCR and lead author of the study, explained that the zeolite itself is not a catalyst. Instead, it enhances the effectiveness of the platinum catalyst by creating a water-rich environment. Liping Liu, a Ph.d. student, and Hongliang Xin, an associate professor at Virginia Tech, further validated this concept through theoretical modeling of the new catalyst system.

“This concept can also apply to other types of zeolites,” Xie added. “It’s a universal strategy.”

Liu emphasized that the pollution reduction method is relatively simple.

“We don’t need to use complicated chemical or other physical processes,” Liu said. “We just mix the two materials — platinum and zeolite — together, run the reaction, and then we see the improvement in activity and selectivity.”

UCR’s Liu, Xie, and Kailong Ye mixed powders of platinum and Y zeolite and provided them to collaborating scientist, Yuejin Li at BASF Environmental Catalyst and Metal Solutions,or ECMS, in Iselin, New Jersey. The powder was made into a thick liquid slurry with binding compounds and applied to the honeycomb structures inside prototype catalytic converters. Scientists from National Synchrotron Light Source II, or NSLS-II, Brookhaven National Laboratory in Upton, New York, were also collaborators.

Liu and Xie expect BASF, which funded the study, to commercialize the technology, which is the subject of a pending patent.

“Well, we are proud,” Xie said. “We’ve developed a new technology to deal with nitrogen oxide emission control, and we think it’s an amazing technique.”

The researchers argue that a sizable proportion of drugs and other compounds can bind to melanin pigments in the skin, leading to differences in how bioavailable and efficacious these drugs and other compounds are in people with varying skin tones.

“Our review paper concludes that melanin, the pigment responsible for skin color, shows a surprising affinity for certain drug compounds,” said Simon Groen, an assistant professor of evolutionary systems biology in the Institute of Integrative Genome Biology at the University of California, Riverside, and a coauthor on the paper. “Melanin’s implications for drug safety and dosing have been largely overlooked, raising alarming questions about the efficacy of standard dosing since people vary a lot in skin tones.”

According to Groen and coauthor Sophie Zaaijer, a consultant and researcher affiliated with UC Riverside who specializes in diversity, equity, and inclusion (DEI) in preclinical R&D and clinical trials, current FDA guidelines for toxicity testing fail to adequately address the impact of skin pigmentation on drug interactions.

“This oversight is particularly concerning given the push for more diverse clinical trials, as outlined in the agency’s Diversity Action Plan,” Zaaijer said. “But current early-stage drug development practices still primarily focus on drug testing in white populations of Northern European descent.”

In one example, the researchers found evidence of nicotine affinity for skin pigments, potentially affecting smoking habits across people with a variety of skin tones and raising questions about the efficacy of skin-adhered nicotine patches for smoking cessation.

“Are we inadvertently shortchanging smokers with darker skin tones if they turn to these patches in their attempts to quit?” Groen said.

Groen and Zaaijer propose utilizing a new workflow involving human 3D skin models with varying pigmentation levels that could offer pharmaceutical companies an efficient method to assess drug binding properties across different skin types.

“Skin pigmentation should be considered as a factor in safety and dosing estimates,” Zaaijer said. “We stand on the brink of a transformative era in the biomedical industry, where embracing inclusivity is not just an option anymore but a necessity.”

According to the researchers, skin pigmentation is just one example. Genetic variations among minority groups can lead to starkly different drug responses across races and ethnicities, affecting up to 20% of all medications, they said.

“Yet, our molecular understanding of these differences remains very limited,” Zaaijer said.

The researchers acknowledge that transformations enhancing inclusivity — encompassing race, ethnicity, sex, and age — demand a comprehensive overhaul of all FDA guidelines on clinical endpoints to align with the FDA’s Diversity Action Plan.

“It’s a monumental task, requiring clear lines of communication between academics, industry researchers, clinicians, and regulators,” Zaaijer said. “The future of medicine relies on our capacity to connect these currently isolated operational teams.”

The researchers point out that a shift towards inclusive drug development is set to take place as instigated by a new law, the Food and Drug Omnibus Reform Act, enacted in 2022.

“The FDA published their draft guidelines recently,” Zaaijer said. “Once final in a few months, they will mandate considering patient diversity in clinical trials and preclinical R&D. The next step is to provide guidance on what pharmacokinetic variables should be tested in drug R&D pipelines in their pursuit to equitable drugs.”

The researchers hope to activate the pharmaceutical industry and academia to start doing systematic experimental evaluations in preclinical research in relation to skin pigmentation and drug kinetics.

They also encourage patients, their advocacy groups, and clinical trial participants to ask questions related to ancestry-specific drug efficacy and safety, such as, “Has this drug been tested to see if it’s safe for people from different ancestral backgrounds, including mine?” Clinicians and pharmaceutical representatives should be able to provide an easy-to-understand document outlining the results of the various tests, the researchers said.

They acknowledge that in the current state of drug development this will be hard.

“In terms of risk profile testing, drugs are most often tested on one or a few human cell models that mostly come from donors of Northern European descent,” Zaaijer said. “Drugs are then tested in a rodent model. If these tests are successful, drug companies push the drug through to clinical trials. But are drugs ready to be given to a diverse patient group if they haven’t first been tested, for example, on human cell models of different ancestries? Would you bungee jump off a bridge if you know the ropes have not been tested for your weight category? Unlikely. So why is this currently acceptable with drugs?”

Groen explained that in different ancestral backgrounds certain genetic variants are more prevalent. Those variants can affect how a drug is metabolized and how it behaves in a body, he said.

“If different ancestral backgrounds are taken into consideration in the early stages of drug discovery, then diverse groups of people may have more trust in the drug development process and enroll in clinical trials because they will be better informed of any potential associated risks,” he said.

The researchers sampled groundwater in two different watersheds adjacent to the Fayetteville Works fluorochemical plant in Bladen County.

“There’s a huge area of PFAS contaminated groundwater — including residential and agricultural land — which impacts the population in two ways,” says David Genereux, professor of marine, earth and atmospheric sciences at NC State and leader of the study.

“First, there are over 7,000 private wells whose users are directly affected by the contamination. Second, groundwater carrying PFAS discharges into tributaries of the Cape Fear River, which affects downstream users of river water in and near Wilmington.”

The researchers tested the samples they took to determine PFAS types and levels, then used groundwater age-dating tracers, coupled with atmospheric contamination data from the N.C. Department of Environmental Quality and the rate of groundwater flow, to create a model that estimated both past and future PFAS concentrations in the groundwater discharging to tributary streams.

They detected PFAS in groundwater up to 43 years old, and concentrations of the two most commonly found PFAS — hexafluoropropylene oxide-dimer acid (HFPO−DA) and perfluoro-2-methoxypropanoic acid (PMPA) — averaged 229 and 498 nanograms per liter (ng/L), respectively. For comparison, the maximum contaminant level (MCL) issued by the U.S. Environmental Protection Agency for HFPO-DA in public drinking water is 10 ng/L. MCLs are enforceable drinking water standards.

“These results suggest it could take decades for natural groundwater flow to flush out groundwater PFAS still present from the ‘high emission years,’ roughly the period between 1980 and 2019,” Genereux says. “And this could be an underestimate; the time scale could be longer if PFAS is diffusing into and out of low-permeability zones (clay layers and lenses) below the water table.”

The researchers point out that although air emissions of PFAS are substantially lower now than they were prior to 2019, they are not zero, so some atmospheric deposition of PFAS seems likely to continue to feed into the groundwater.

“Even a best-case scenario — without further atmospheric deposition — would mean that PFAS emitted in past decades will slowly flush from groundwater to surface water for about 40 more years,” Genereux says. “We expect groundwater PFAS contamination to be a multi-decade problem, and our work puts some specific numbers behind that. We plan to build on this work by modeling future PFAS at individual drinking water wells and working with toxicologists to relate past PFAS levels at wells to observable health outcomes.”