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Spinal Injuries Throw Body Clocks Off-Schedule, New Study Shows

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In the hours and days following a spinal cord injury, the gears that control the body’s internal clocks fall profoundly out of sync, impacting body temperature, hormone fluctuation, immunity and the timing of a host of other bodily processes, according to new CU Boulder research.

The study, funded by the U.S. Department of Defense and published Monday in the journal eNeuro, is among the first to comprehensively assess how spinal injury impacts circadian rhythms, or the 24-hour-cycles of physiological processes. If replicated in humans, the findings could lead to new “chronotherapies” to reset off-kilter clocks and potentially improve long-term recovery.

It could also have implications for stroke and traumatic brain injury patients, the authors say.

“People often think of the effects of spinal cord injury in terms of the physical tissue damage itself,” said senior author Linda Watkins, a distinguished professor of Behavioral Neuroscience at CU Boulder.

“The surprising and important finding here is that localized tissue damage fundamentally changes the rhythms of life.”

Previous research has shown that in the aftermath of spinal cord injury people often have trouble regulating their body temperature and experience suppressed immunity. Longer term, they tend to have chronic sleep problems and impaired metabolism. But little is known about how such injuries impact the broader circadian system, said lead author Andrew Gaudet, who conducted the study while a postdoctoral researcher in Watkins’ lab.

Molecular clocks out of sync

“Every single cell in our body has its own molecular clock, including all the machinery required for the body to know what time it is,” said Gaudet.

“We wanted to know how spinal cord injury impacts the mediators that influence those clocks and the clocks themselves.”

The researchers studied rats in the immediate aftermath of a moderate injury to the thoracic, or middle, spinal cord. They measured body temperature, activity levels and blood levels of a stress hormones called glucocorticoids. They also looked at expression of genes which control the circadian clock in the spinal cord and influence immune response, including inflammation, throughout the body.

“We found that all of these mediators of the circadian system were strongly disrupted soon after injury and slowly returned to normal measures only after a few weeks,” said Gaudet, now an assistant professor of psychology and neurology at the University of Texas

For instance, two days after the injury, glucocorticoid levels were up to 250 percent higher than normal. One week after injury, their rhythms were still irregular, peaking during sleep rather than in the active time of day.

Six days after injury, their core temperature remained higher than normal when they were inactive. Up to 30 days after injury, their temperature was still peaking 2 to 4 hours earlier than normal. Feeding patterns were also impacted. After 14 to 42 days, most patterns returned to normal.

Analysis of tissue from the injury site also found that expression of clock genes was “remarkably reduced” as was expression of genes that influence the body’s ability to heal. Surprisingly, the researchers also found reduced clock gene expression in uninjured tissue elsewhere.

Gaudet explains that while light is the primary timekeeper (or “president”) of the circadian system, temperature, activity levels, and hormone levels serve as “middle managers” assuring that all the other clocks run on time.

“If they are off-schedule it can make the other clocks run improperly and that can influence a whole host of body processes,” he said.

“This could have implications for recovery.”

Chronotherapies on the horizon

He cautions that more research is needed to determine whether the findings translate to people.

If so, circadian-related therapies could ultimately become part of the treatment tool box.

This might involve having a window in patients’ rooms so they can be exposed to bright natural light in the mornings, scheduling meals, sleep, rehabilitation and surgery at optimal times of day, and assuring that the environment in the intensive care unit at night is kept as dark as possible with minimal interruptions.

Similar approaches could be taken for patients with traumatic brain injury, stroke and neurological disorders which also may alter the clock, the researchers note.

“Just recognizing that the function of many clocks is disrupted by spinal cord injury suggests that doing simple things to reset those clocks might help,” says Watkins.

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Report Reveals Link Between Air Pollution And Increased Risk For Miscarriage

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Air quality has been associated with numerous adverse health outcomes from asthma to pre-term birth. Researchers at University of Utah Health found women living along the Wasatch Front — the most populous region in the state of Utah — had a higher risk (16 percent) of miscarriage following short-term exposure to elevated air pollution. The results are available online on December 5 in the journal Fertility and Sterility.

“Not being from Salt Lake originally, I noticed a pattern in the relation to air quality and pregnancy loss,” said Matthew Fuller, M.D., assistant professor of Surgery at U of U Health and senior author on the paper.

“I knew this was an understudied question so we decided to dig deeper.”

Fuller joined University of Utah research analyst Claire Leiser on a retrospective study consisting of more than 1,300 women (54 percent Caucasian, 38 percent Hispanic, and other/missing 8 percent; average age 28 years). The women in the study sought help at the U of U emergency department following a miscarriage (up to 20-weeks gestation) between 2007 to 2015.

The team examined the risk of miscarriage during a three- or seven-day window following a spike in the concentration of three common air pollutants: small particulate matter (PM 2.5), nitrogen dioxide and ozone. The study excluded women who lived outside Utah.

“We are really only seeing the most severe cases during a small window of time,” said Leiser, first author on the paper.

“These results are not the whole picture.”

Leiser notes the results suggest there could be an increased risk for an individual. Their research only captured women who sought help at an emergency department at one hospital in the region. It does not account for women who may have sought outpatient care through their obstetric or primary care providers.

The team found a slight increased risk in miscarriage for women exposed to elevated levels of nitrogen dioxide (16 percent for 10 ppb increase during the seven-day window). Although small particulate matter does track with nitrogen dioxide, these results did not significantly associate with an increased risk of miscarriage.

“While we live in a pretty unique geographic area, the problems we face when it comes to air pollution are not unique,” said Fuller.

“As the planet warms and population booms, air pollution is going to become a bigger problem not only in the developing world but across the United States.”

The Wasatch Front experiences short-periods of poor air quality, primarily during the winter months, when inversions trap pollutants close to the ground (for the 7-day window: PM2.5 min = 0.3 μg/m3; PM2.5 max = 73.0 μg/m3; O3 min = 4 ppb; O3 max= 80 ppb; NO2min = 0.5 ppb; NO2 max = 65 ppb). The researchers tracked air quality by zip code, establishing six designated air basins within the Wasatch Front. They compared air quality in each basin to their patients’ outcomes.

The team conducted a case cross-over study that estimated a woman’s risk of miscarriage multiple times in a month where air pollution exposure varied. This approach removed other risk factors, like maternal age, from the study. The scientists were unable to ascertain the age of the fetus at the time of the miscarriage and were unable pinpoint a critical period when the fetus may be most vulnerable to pollutants.

“The results of this study are upsetting, and we need to work together as a society to find constructive solutions,” Fuller said.

Fuller recommends women speak with their doctor about any health concerns. Women can manage the risk by using a N95 particulate respirator face mask to filter out pollutants or avoid outdoor physical activity on poor air quality days. Women can also use filters to lower indoor pollution and, if possible, time conception to avoid seasonal episodes of poor air quality.

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Alcohol Intake May Be Key to Long-term Weight Loss for People with Diabetes

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Research shows that losing weight can help prevent or delay the onset of diabetes. While best practice for weight loss often includes decreasing or eliminating calories from alcohol, few studies examine whether people who undergo weight loss treatment report changes in alcohol intake and whether alcohol influences their weight loss.

A new study from the University of Pennsylvania School of Nursing (Penn Nursing) suggests that alcohol consumption may attenuate long-term weight loss in adults with Type 2 diabetes.

In the study, close to 5,000 people who were overweight and had diabetes were followed for four years. One group participated in Intensive Lifestyle Intervention (ILI) and the other in a control group consisting of diabetes support and education. Data showed that participants in the ILI group who abstained from alcohol consumption over the four-year period lost more weight than those who drank any amount during the intervention. Results from the study also showed that heavy drinkers in the ILI group were less likely to have clinically significant weight loss over the four years.

“This study indicates that while alcohol consumption is not associated with short‐term weight loss during a lifestyle intervention, it is associated with worse long‐term weight loss in participants with overweight or obesity and Type 2 diabetes,” says lead investigator Ariana M. Chao, PhD, CRNP, Assistant Professor of Nursing in the Department of Biobehavioral Health Sciences.

“Patients with Type 2 diabetes who are trying to lose weight should be encouraged to limit alcohol consumption.”

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Hang In There. As Couples Age, Humor Replaces Bickering

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Honeymoon long over? Hang in there. A new UC Berkeley study shows those prickly disagreements that can mark the early and middle years of marriage mellow with age as conflicts give way to humor and acceptance.

Researchers analyzed videotaped conversations between 87 middle-aged and older husbands and wives who had been married for 15 to 35 years, and tracked their emotional interactions over the course of 13 years. They found that as couples aged, they showed more humor and tenderness towards one another.

Overall, the findings, just published in the journal Emotion, showed an increase in such positive behaviors as humor and affection and a decrease in negative behaviors such as defensiveness and criticism. The results challenge long-held theories that emotions flatten or deteriorate in old age and point instead to an emotionally positive trajectory for long-term married couples.

“Our findings shed light on one of the great paradoxes of late life,” said study senior author Robert Levenson, a UC Berkeley psychology professor.

“Despite experiencing the loss of friends and family, older people in stable marriages are relatively happy and experience low rates of depression and anxiety. Marriage has been good for their mental health.”

Consistent with previous findings from Levenson’s Berkeley Psychophysiology Laboratory, the longitudinal study found that wives were more emotionally expressive than their husbands, and as they grew older they tended toward more domineering behavior and less affection. But generally, across all the study’s age and gender cohorts, negative behaviors decreased with age.

“Given the links between positive emotion and health, these findings underscore the importance of intimate relationships as people age, and the potential health benefits associated with marriage,” said co-lead author Alice Verstaen, who conducted the study as a Ph.D. student at UC Berkeley and is currently a postdoctoral fellow at the VA Puget Sound Health Care System.

The results are the latest to emerge from a 25-year UC Berkeley study headed by Levenson of more than 150 long-term marriages. The participants, now mostly in their 70s, 80s and 90s, are heterosexual couples from the San Francisco Bay Area whose relationships Levenson and fellow researchers began tracking in 1989.

In their investigation of marital relationships, researchers viewed 15-minute interactions between spouses in a laboratory setting as they discussed shared experiences and areas of conflict. They tracked the emotional changes every few years.

The spouses’ listening and speaking behaviors were coded and rated according to their facial expressions, body language, verbal content and tone of voice. Emotions were coded into the categories of anger, contempt, disgust, domineering behavior, defensiveness, fear, tension, sadness, whining, interest, affection, humor, enthusiasm and validation.

Researchers found that both middle-aged and older couples, regardless of their satisfaction with their relationship, experienced increases in overall positive emotional behaviors with age, while experiencing a decrease in overall negative emotional behaviors.

“These results provide behavioral evidence that is consistent with research suggesting that, as we age, we become more focused on the positives in our lives,” Verstaen said.

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