The researchers compared various time windows of exposure, finding that the previous decade of water arsenic exposure up to the time of a cardiovascular disease event contributed the greatest risk. The findings are published in the journal Environmental Health Perspectives.

“Our findings shed light on critical time windows of arsenic exposure that contribute to heart disease and inform the ongoing arsenic risk assessment by the EPA. It further reinforces the importance of considering non-cancer outcomes, and specifically cardiovascular disease, which is the number one cause of death in the U.S. and globally,” said Danielle Medgyesi, a doctoral Fellow in the Department of Environmental Health Sciences at Columbia Mailman School. “This study offers resounding proof of the need for regulatory standards in protecting health and provides evidence in support of reducing the current limit to further eliminate significant risk.”

According to the American Heart Association and other leading health agencies, there is substantial evidence that arsenic exposure increases the risk of cardiovascular disease. This includes evidence of risk at high arsenic levels (>100µg/L) in drinking water. The U.S. Environmental Protection Agency reduced the maximum contaminant level (MCL) for arsenic in community water supplies (CWS) from 50µg/L to 10µg/L beginning in 2006. Even so, drinking water remains an important source of arsenic exposure among CWS users. The natural occurrence of arsenic in groundwater is commonly observed in regions of New England, the upper Midwest, and the West, including California.

To evaluate the relationship between long-term arsenic exposure from CWS and cardiovascular disease, the researchers used statewide healthcare administrative and mortality records collected for the California Teachers Study cohort from enrollment through follow-up (1995-2018), identifying fatal and nonfatal cases of ischemic heart disease and cardiovascular disease. Working closely with collaborators at the California Office of Environmental Health Hazard Assessment (OEHHA), the team gathered water arsenic data from CWS for three decades (1990-2020).

The analysis included 98,250 participants, 6,119 ischemic heart disease cases and 9,936 CVD cases. Excluded were those 85 years of age or older and those with a history of cardiovascular disease at enrollment. Similar to the proportion of California’s population that relies on CWS (over 90 percent), most participants resided in areas served by a CWS (92 percent). Leveraging the extensive years of arsenic data available, the team compared time windows of relatively short-term (3-years) to long-term (10-years to cumulative) average arsenic exposure. The study found decade-long arsenic exposure up to the time of a cardiovascular disease event was associated with the greatest risk, consistent with a study in Chile finding peak mortality of acute myocardial infarction around a decade after a period of very high arsenic exposure. This provides new insights into relevant exposure windows that are critical to the development of ischemic heart disease.

Nearly half (48 percent) of participants were exposed to an average arsenic concentration below California’s non-cancer public health goal <1 µg/L. In comparison to this low-exposure group, those exposed to 1 to <5 µg/L had modestly higher risk of ischemic heart disease, with increases of 5 to 6 percent. Risk jumped to 20 percent among those in the exposure ranges of 5 to <10 µg/L (or one-half to below the current regulatory limit), and more than doubled to 42 percent for those exposed to levels at and above the current EPA limit ≥10µg/L. The relationship was consistently stronger for ischemic heart disease compared to cardiovascular disease, and no evidence of risk for stroke was found, largely consistent with previous research and the conclusions of the current EPA risk assessment.

These results highlight the serious health consequences not only when community water systems do not meet the current EPA standard but also at levels below the current standard. The study found a substantial 20 percent risk at arsenic exposures ranging from 5 to <10 µg/L which affected about 3.2 percent of participants, suggesting that stronger regulations would provide significant benefits to the population. In line with prior research, the study also found higher arsenic concentrations, including concentrations above the current standard, disproportionally affect Hispanic and Latina populations and residents of lower socioeconomic status neighborhoods.

“Our results are novel and encourage a renewed discussion of current policy and regulatory standards,” said Columbia Mailman’s Tiffany Sanchez, senior author. “However, this also implies that much more research is needed to understand the risks associated with arsenic levels that CWS users currently experience. We believe that the data and methods developed in this study can be used to bolster and inform future studies and can be extended to evaluate other drinking water exposures and health outcomes.”

Co-authors are Komal Bangia, Office of Environmental Health Hazard Assessment, Oakland, California; James V. Lacey Jr and Emma S. Spielfogel,California Teacher Study, Beckman Research Institute, City of Hope, Duarte, California; and Jared A Fisher^, Jessica M. Madrigal, Rena R. Jones, and Mary H. Ward^, Division of Cancer Epidemiology and Genetics, National Cancer Institute.

The study was supported by the National Cancer Institute, grants U01-CA199277, P30-CA033572, P30-CA023100, UM1-CA164917, and R01-CA077398; and also funded by the Superfund Hazardous Substance Research and Training Program P42ES033719; NIH National Institute of Environmental Health Sciences P30 Center for Environmental Health and Justice P30ES9089, NIH Kirschstein National Research Service Award Institutional Research Training grant T32ES007322, NIH Predoctoral Individual Fellowship F31ES035306, and the Intramural Research Program of the NCI Z-CP010125-28.

“While exposure to persecution, war and displacement is associated with high rates of psychological disorders, such as PTSD and depression, remarkably the majority of refugees, despite having gone through very difficult experiences, don’t go on to develop a psychological disorder,” says Prof. Nickerson, Director of the Refugee Trauma and Recovery Program at UNSW’s School of Psychology.

Despite this, previous research has focused on trying to understand factors that predict psychopathology or psychological distress, rather than factors that predict wellbeing or resilience.

“More recently, however, there has been a movement towards a strengths-based approach in mental health, particularly in the refugee space, and we wanted to look at what research was out there,” says Prof. Nickerson.

The paper, out this week in Nature Mental Health, is the first to focus on factors contributing to better mental health in refugees.

To conduct the review, researchers searched four databases for relevant studies. They screened thousands of studies, 174 of which met the study criteria. 81% of the included papers were undertaken in refugees living in high-income countries (HICs) and 19% in lower-and-middle income countries (LMICs).

“The lack of research looking at predictors of good mental health highlighted the deficit focus of so much research into refugee mental health,” says Prof. Nickerson. She also noted that though 75% of the world’s refugees live in LMICs, most of the research took place in HICs.

“It underscores a real gap in refugee research,” says Prof. Nickerson.

What were the researchers looking for?

“Our systematic review covered studies investigating the mental health of refugees or asylum seekers, and we looked at factors that we called either protective or promotive of mental health. Protective factors are associated with reduced poor mental health outcomes, and promotive factors are associated with increased good mental health outcomes,” says Prof. Nickerson.

The researchers wanted to understand how to enhance the strengths of an individual or community to alleviate or even prevent distress.

“We were interested in everything from demographic and social factors to environmental and psychological factors,” Prof. Nickerson says.

“We wanted to be able to speak to a range of different implications and recommendations in the field of refugee mental health — from what psychologists or social workers might do with a client in a room, and also more broadly what kinds of conditions policy-makers should be creating in countries that host refuges to help people thrive and move forward after traumatic experiences.”

Study findings

The refugee experience is characterised by protracted exposure to danger and uncertainty. The review highlighted factors related to stability and predictability as having some of the strongest associations with good mental health in refugees.

“It makes a lot of sense that, if people who’ve been through very difficult experiences are going to overcome those and thrive, we need to create conditions where their basic needs for safety are met,” says Prof. Nickerson.

The study found a secure visa status, employment, income, good housing conditions and control over environmental circumstances were associated with good mental health outcomes in both HICs and/or LMICs.

Individuals vary in their capacity to cope with difficult circumstances, with resilience reflecting the extent to which an individual can recover or maintain good mental health in the context of adversity.

The review found that psychological factors such as cognitive strategies, self-efficacy and a sense of control were protective and promotive of wellbeing.

Building individual skills and capabilities to cope and thrive represents an important goal to promote good mental health in refugees.

“When we’re trying to understand how best to support people, we often look at the things that are going wrong, and that means our interventions are focused on those things. This study speaks to the importance of harnessing interventions that are associated with resilience, self-efficacy and psychological flexibility,” says Prof. Nickerson.

But experiences such as war, persecution and displacement occur at a societal level, and so approaches to promoting good mental health in their aftermath must extend beyond the individual.

“There is a consistent link between social engagement and support and good mental health outcomes among refugees, particularly for those in high-income countries,” Prof. Nickerson says.

“The ability to communicate in the host language, social support, and social engagement with both the refugees’ own community and the host community, along with religious coping strategies, were all linked with increased wellbeing.”

The way ahead

This review puts forward a clear research agenda, with at least three important pathways to progressing our understanding of refugee mental-health wellbeing, Prof. Nickerson says.

“One is to purposefully study factors associated with wellbeing and positive mental health outcomes, rather than just looking at factors that contribute to psychological distress. Refugee communities are remarkably resilient, and we have a lot to learn from people who have overcome adversity to thrive in their new country.

“Two is to fill the research gap in low-and-middle-income countries. The majority of refugees live in transit settings outside high-income countries. If we are going to provide effective supports, we need to understand factors that promote wellbeing in these contexts

“And finally it’s important to take a cross-disciplinary research approach. By bringing together researchers, psychologists, social workers and policy-makers, we can gain a more nuanced understanding of protective and promotive factors. Having refugee voices at the centre of this process is critical to help us understand priority areas for research and using these findings effectively. This will pave the way for developing policies and interventions that support refugee communities to thrive.”

This research was supported by funding from the Social Policy Group.

When a virus attacks, the body’s immune response has two basic layers of defense: the innate and the adaptive immune systems. While the adaptive immune system grows stronger against a specific pathogen as the body is exposed to it multiple times and which forms the basis of vaccinations, the innate immune system is an assortment of molecular mechanisms that work against a broad range of pathogens at a basic level. The Kobe University virologist SHOJI Ikuo says, “The new coronavirus, however, is so infectious that we wondered what clever mechanisms the virus employs to evade the innate immune system so effectively.”

Shoji’s team previously worked on the immune response to hepatitis viruses and investigated the role of a molecular tag called “ISG15” the innate immune system attaches to the virus’s building blocks. Having learned that the novel coronavirus has an enzyme that is especially effective in removing this tag, he decided to use his team’s expertise to elucidate the effect of the ISG15 tag on the coronavirus and the mechanism of the virus’s countermeasures.

In a paper in the Journal of Virology, the Kobe University-led team is now the first to report that the ISG15 tag gets attached to a specific location on the virus’s nucleocapsid protein, the scaffold that packages the pathogen’s genetic material. For the virus to assemble, many copies of the nucleocapsid protein need to attach to each other, but the ISG15 tag prevents this, which is the mechanism behind the tag’s antiviral action. “However, the novel coronavirus also has an enzyme that can remove the tags from its nucleocapsid, recovering its ability to assemble new viruses and thus overcoming the innate immune response,” explains Shoji.

The novel coronavirus shares many traits with the SARS and MERS viruses, which all belong to the same family of viruses. And these viruses, too, have an enzyme that can remove the ISG15 tag. However, Shoji’s team found that their versions are less efficient at it than the one in the novel coronavirus. And in fact, it has been reported recently that the previous viruses’ enzymes have a different primary target. “These results suggest that the novel coronavirus is simply better at evading this aspect of the innate immune system’s defense mechanism, which explains why it is so infectious,” says Shoji.

But understanding just why the novel coronavirus is so effective also points the way to developing more effective treatments. The Kobe University researcher explains: “We may be able to develop new antiviral drugs if we can inhibit the function of the viral enzyme that removes the ISG15 tag. Future therapeutic strategies may also include antiviral agents that directly target the nucleocapsid protein, or a combination of these two approaches.”

This research was funded by the Kansai Economic Federation, the Hyogo Science and Technology Association (grant 3501) and the Ministry of Education, Culture, Sports, Science and Technology Japan (grant 18042-203556). It was conducted in collaboration with researchers from Universitas Gadjah Mada, Niigata University, the University of Yamanashi, Hokkaido University and Osaka University.

The term kokumi derives from Japanese and refers to a full-bodied and long-lasting taste experience. The taste impression is particularly pronounced in aged cheeses, mainly due to the increasing concentration of gamma-glutamyl dipeptides. These are small molecules that consist of a link between glutamic acid and another amino acid.

Depending on how the two amino acids are linked, researchers distinguish between gamma-, alpha-, and X-glutamyl dipeptides, with the latter two not contributing to the kokumi effect. The high polarity of the glutamyl dipeptides, as well as their great structural similarity with different flavor contributions, represent a major challenge for food analysis.

Efficient analysis method developed

Nevertheless, the team led by principal investigator Andreas Dunkel of the Leibniz Institute has succeeded in developing a new efficient analysis method based on ultra-high performance liquid chromatography-mass spectrometry. For the first time, it can precisely and selectively determine the concentrations of all 56 gamma-glutamyl dipeptide variants in just 22 minutes. Optimized sample preparation makes it possible to analyze 60 cheese samples per day.

“This is a significant improvement compared to other methods. Our tests have shown that our method is faster, more efficient, and yet reliable — it delivers reproducible results and detects even the smallest concentrations,” says first author Sonja Maria Fröhlich, a doctoral student at the Leibniz Institute. To further investigate the influence of ripening time on gamma-glutamyl dipeptide concentrations, the researchers applied the method to 122 cheese samples from Europe and the USA after the test phase. The ripening times of the cheese ranged from two weeks to 15 years.

Mold cultures accelerate flavor development

The results show that, as expected, the concentrations of glutamyl dipeptides increase with increasing ripeness. “Interestingly, the addition of blue and white mold cultures led to significantly higher gamma-glutamyl dipeptide concentrations, even at shorter ripening times,” says Andreas Dunkel, who heads the Integrative Food Systems Analysisresearch group at the Leibniz Institute.

The food chemist adds: “The concentration profiles we have determined for different stages of ripening and different types of cheese can be used in the future as a database for prediction models. The latter could, for example, be used to objectively monitor flavor development during cheese ripening, to shorten ripening times, or to develop new plant-based cheese products with high consumer acceptance.”

“In the sense of an interdisciplinary, food systems biology research approach, one of our goals is to combine analytical research results with bioinformatic methods to develop predictive models suitable to support sustainable food production. This is also the starting point of the project led by Andreas Dunkel,” concludes Veronika Somoza, director of the Leibniz Institute.

However, Van Overwalle’s research extends beyond motor functions, exploring the cerebellum’s involvement in social and cognitive abilities. His findings reveal that abnormalities in the cerebellum not only lead to motor deficits but are also linked to emotional and behavioral disorders. He references research on individuals with autism, demonstrating how non-invasive brain stimulation techniques like magnetic stimulation can improve social task performance.

“We’ve seen improvements in the sequence of cognitive tasks in people with autism through magnetic stimulation,” says Van Overwalle. “We’re now testing more complex tasks to see if these effects can be further enhanced, with the ultimate goal of developing practical treatments for people with autism.”

A notable breakthrough is the use of transcranial electrical stimulation (tES), a more affordable and accessible technique compared to magnetic stimulation. While the effects of tES are still limited, the research group is committed to further development, seeing its potential for wide-scale application in the future.

This research offers a fresh perspective on the cerebellum’s role and paves the way for new treatments for psychiatric and neurological conditions, such as autism spectrum disorders. “Our hope is to refine these techniques further to improve social and cognitive functions in people with autism,” concludes Van Overwalle.