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Category Archives: Rhythmic Human
Well, it’s Thanksgiving tomorrow night so it’s time to republish this post from last year, just in time for the ageless debate: does eating turkey meat make you sleepy? Some people say Yes, some people say No, and the debate can escalate into a big fight. The truth is – we do not know.
But for this hypothesis to be true, several things need to happen. In this post I look at the evidence for each of the those several things. Unfortunately, nobody has put all the elements together yet, and certainly not in a human. I am wondering…is there a simple easily-controlled experiment that people can do on Thursday night, then report to one collecting place (e.g., a blog) where someone can do the statistics on the data and finally lay the debate to rest? Any ideas?
Also, I will add the comments that the post originally received and I hope for new comments from people with relevant expertise. Is Trp Hxlse really a rate-limiting enzyme? If so, why gavaging chickens and rats with Try increases plasma melatonin? Is it different in humans? You tell me!
(originally posted on November 25, 2005)
Apparently, the timing of sporting events in Beijing, probably driven by needs of American TV audiences, did not take into consideration the best time of day for athletic performance. But who cares about athletes, or even about breaking Olympic and world records, when delivering Joe Schmoe to the Budweiser commercial is much, much more important for the success of Olumpic games?!
This article provides a nice summary of the issue and the current state of understanding of the way circadian clocks affect athletic performance:
Science Says Athletes Perform Better At Night
This week’s Ask a ScienceBlogger question is:
A reader asks: Is severely regulating your diet for a month each year, as Muslims do during Ramadan, good for you?
There is no way I can get out of this one! As far as I know, I am the only one here who actually did research on fasting! Mind you, it’s been about 5 years since I last delved deep into the literature on the effects of fasting and feeding on various body functions, mainly body temperature and circadian rhythms, but I can try to pull something out of my heels now.
I tend to rant about sleep in adolescents for various reasons, but other people focus on other age groups. Infants are one such group, interesting because it takes a while for their circadian rhythms to consolidate resulting in “sleeping through the night”.
For years, the only serious book on the topic was Ferber, much maligned for its advice to “let them cry it out”, though the rest of the book is correct and informative. Apparently, there is a good new book on the topic – The No-Cry Sleep Solution: Gentle Ways to Help Your Baby Sleep Through the Night (as well as The No-Cry Sleep Solution for Toddlers and Preschoolers by the same author, Elizabeth Pantley).
Also, Ferber has issued a new edition of his book in which he gives up on the “cry it out” strategy and gives more space to the issue of bed sharing.
Bill Bailey reports that an organization called ‘Screening for Mental Health’ offers free screenings for Seasonal Affective Disorder (SAD). But then, they push drugs on people they “diagnose”. The only problem – SAD is not treated with drugs!!! It is a circadian disorder, treated with light therapy and behavioral therapy. Quacks!
According to Dr. Iman Sharif, the results were clear-cut. “On weekdays, the more they watched, the worse they did,” said Dr. Sharif. Weekends were another matter, with gaming and TV watching habits showing little or no effect on academic performance, as long as the kids spent no more than four hours per day in front of the console or TV. “They could watch a lot on weekends, and it didn’t seem to correlate with doing worse in school,” noted Dr. Sharif.
The study was using self-reporting by kids, which has its problems, but is OK in this case, I think. The key information they did not gather was the timing of game-playing and TV watching.
On schooldays, the only time they can do this is late in the evening, after homework and dinner and sports and everything else have been done. Exposure to light from the screens, as well as the emotional involvement (perhaps raised adrenaline?) phase-delays the kids’ already delayed circadian clocks. Instead of getting 9 hours of sleep, they get 5 or 6. Of course they perform miserably at school and the athletic field, feel lousy and misbehave – they are chronically sleep-deprived.
On weekends, kids are likely to play and watch in the morning or early afternoon, which does not affect the phase of their sleep-wake cycle.
I let my kids play games first thing when they come home from school. They do homework later – it gradually puts them to sleep so they are not sleep deprived.
Hat-tip: Ed Cone.
A new study at the Université de Montréal has concluded that people drinking coffee to get through a night shift or a night of studying will strongly hurt their recovery sleep the next day. The study published in the current issue of Neuropsychopharmacology was conducted by Dr. Julie Carrier from the Department of Psychology at the Université de Montréal. Dr. Carrier runs the Chronobiology Laboratory at the Hôpital du Sacré-Coeur de Montréal.
“We already knew that caffeine has important effects on nocturnal sleep. It increases the time taken to fall asleep, it increases the amount of awakenings, and it decreases the amount of deep sleep. We have shown that these effects of caffeine on sleep are way stronger when taken at night prior to a daytime recovery sleep episode than in the evening before a nocturnal sleep episode.”
“Caffeine makes daytime sleep episodes too shallow to override the signal from the biological clock that tells the body it should be awake at this time of day,” explains Dr. Carrier. “We often use coffee and other sources of caffeine during the nighttime to counteract sleepiness generated by sleep deprivation, jet lag, and shift-work. However, this habit may have important effects when you then try to recuperate during daytime.”
Thirty-four moderate caffeine consumers participated in both caffeine (200 mg) and placebo (lactose) conditions in a double-blind crossover design. Seventeen subjects followed their habitual sleep–wake cycle and slept in the laboratory during the night (Night), while 17 subjects were sleep deprived for one night and recovery sleep started in the morning (DayRec). All subjects received a capsule of 100 mg of caffeine (or placebo) 3 hours before bedtime, and the remaining dose 1 hour before bedtime. Compared to placebo, caffeine lengthened sleep latency, increased stage 1, and reduced stage 2 and slow-wave sleep (SWS) in both groups. However, caffeine reduced sleep efficiency more strongly in the DayRec group, and decreased sleep duration and REM sleep only in that group.
A recent analysis of national survey data reveals that over 1.6 million American adults use some form of complementary and alternative medicine (CAM) to treat insomnia or trouble sleeping according to scientists at the National Center for Complementary and Alternative Medicine (NCCAM), part of the National Institutes of Health.
Those using CAM to treat insomnia or trouble sleeping were more likely to use biologically based therapies (nearly 65 percent), such as herbal therapies, or mind-body therapies (more than 39 percent), such as relaxation techniques. A majority of people who used herbal or relaxation therapies for their insomnia reported that they were helpful. The two most common reasons people gave for using CAM to treat insomnia were they thought it would be interesting to try (nearly 67 percent) and they thought CAM combined with a conventional treatment would be helpful (nearly 64 percent).
I don’t really know what to think. On one hand, someone is making a lot of money on this. On the other hand, placebo effect may be quite effective for relaxing a person enough to fall asleep. Meditation certainly will help a person relax – it is so boring you have to fall asleep after a while. And who knows, one of those therapies may actually have some effectiveness after all – we don’t know because it was never tested. On the other hand, many herbal remedies, because they are never tested and approved, may contain some nasty chemicals that can kill you. Such deadly molecules were discovered in some brands of melatonin a few years back. So, they are not safe even if they are effective. I’d like to see Orac and Abel comment on this.
In addition to looking at the data on CAM use and insomnia, the researchers also looked at the connection between trouble sleeping and five significant health conditions: diabetes, hypertension, congestive heart failure, anxiety and depression, and obesity. They found that insomnia or trouble sleeping is highly associated with four of the five conditions: hypertension, congestive heart failure, anxiety and depression, and obesity.
All of those connecitons have been seen before and some of those have been studied in quite a lot of detail. Unfortunately, there appears to be a vicious cycle – these conditions negatively affect sleep and lack of sleep negatively affects these conditions.
So, is extreme “larkiness” due to overphosphorilation or underphosphorilation of PERIOD2?
Hypotheses get tested, studies conflict with each other and, in the end, there is a resolution. In this case, we are still waiting for resolution. Science marches on.
Mrs. Mattingly highlighted the major components of the college preparatory curriculum that fills the school day beginning at 8:50 a.m. and continues until 5 p.m. The hours are designed to accommodate teens’ circadian rhythms.
College students may believe they are being more productive when they sleep less, but in reality it is causing harm to their bodies. The National Sleep Foundation points out that receiving less than six hours of sleep a night is associated with 1.7 times greater risk of disease, according to http://www.sleepfoundation.org. The chance of decreased academic performance, driving accidents, colds and flu and mental illnesses are all increased.
Fatigue is worsened when lack of sleep is coupled with a disruption to the body’s circadian rhythm, which regulates high and low energy periods throughout the day – common among flight and ground crews as well as controllers.
And it’s also magnified by jetlag. One U.S. sleep researcher estimates 96 per cent of airline pilots and flight attendants operate in a permanent state of jetlag.
“On our mission, with where the sun is, we have 55 minutes of daylight followed by 75 minutes of darkness … and that does affect your circadian rhythm,” MacLean replied.
Earlier this year, during the National Sleep Awareness Week, I wrote a series of posts about the changes in sleep schedules in adolescents. Over the next 3-4 hours, I will repost them all, starting with this one from March 26, 2006. Also check my more recent posts on the subject here and here…
This kind of ignorant bleating makes me froth at the mouth every time – I guess it is because this is my own blogging “turf”.
One of the recurring themes of my blog is the disdain I have for people who equate sleep with laziness out of their Puritan core of understanding of the world, their “work ethic” which is a smokescreen for power-play, their vicious disrespect for everyone who is not like them, and the nasty feeling of superiority they have towards the teenagers just because they are older, bigger, stronger and more powerful than the kids. Not to forget the idiotic notions that kids need to be “hardened”, or that, just because they managed to survive some hardships when they were teens, all the future generations have to be sentenced to the same types of hardships, just to make it even. This is bullying behavior, and disregarding and/or twisting science in the search for personal triumphalism irks me to no end.
I hated getting up early, too. I still hate it, and I’m so far beyond growth hormones that I don’t even remember how they felt. But I do remember that in middle and high school, I dragged myself out of the house at 5 a.m. every day of the week to deliver papers before I caught the 6:45 a.m. bus to school. I never fell asleep in class. Neither did anybody else. And something caused me to grow 6 inches and add 35 pounds between sophomore and junior year. At the end of that kind of day, complete with cross-country, basketball or track, I had no trouble falling asleep at 10 p.m.
He said that he grew up in height and weight when he was in high school. Who knows how much more he would have grown if he was not so sleep deprived (if his self-congatulatory stories are to be believed and he did not slack off every chance he had). Perhaps he would not grow up to be so grouchy and mean-spirited if he had a more normal adolescence.
I don’t know where he got the idea that growth hormone is a cause of the phase-delay of circadian rhythms in adolescence. It could be, but it is unlikely – we just don’t know yet. But, if a hormone is a cause, than it is much more likely to be sex steroids. Perhaps his sleep-deprived and testosterone-deprived youth turned him into a sissy with male anxiety he channels into lashing at those weaker than him?
In previous centuries, adolescents in an agrarian society got up at 4:30 or 5 a.m. with their parents to milk the cows or do any other of a long list of chores. Did growth hormones pass them by? Where were the “studies” that showed they really needed to go to bed after midnight and sleep until 10? And why weren’t their parents all being reported to the DSS? Oh, that’s right, there was no DSS. How did that generation survive?
He assumes that in times before electricity, teenagers used to wake up and fall asleep at the same time adults did. Well, they did not. Studies of sleep patterns in primitive tribes show that adolescents are the last ones to wake up (and nobody bashes them for it – it is the New Primitives with access to media that do that) and the last ones to fall asleep – they serve as first-shift sentries during the night watch.
Even in this, the 21st century, kids who enter the military at 17 find that they can fall asleep easily at 9:30 or 10, because they know they’re going to be getting up at 4:30 or 5. Apparently the Army hasn’t read the study on circadian rhythms.
Actually, the military being the most worried by this problem is funding a lot of research on circadian rhythms and sleep and has been for decades. Because they know, first hand, how big a problem it is and that yelling sargeants do not make alert soldiers.
Kids, if you need more sleep, my study shows there’s a simple way to get it. Turn off – I mean “power down” – the cell phone, the iPod and the computer sometime before 11 p.m. Turn off the TV. Turn off the light. Lie down in bed and close your eyes.
…and sit in the dark for the next four hours, heh?
This being the beginning of the school year, I can expect to see more of such nonsense printed in the MSM and on blogs soon, so I may repost (tomorrow) some of the stuff I have already written against the societal equation of sleep with laziness in general, as well as specifically concerning adolescents (see this, this, this, this and this, for instance).
What especially drives me crazy is that so many teachers, people who work with adolescents every day, succumb to this indulgence in personal power over the children. It is easier to get into a self-righteous ‘high’ than to study the science and do something about the problem. It is easier to blame the kids than to admit personal impotence and try to do something about it by studying the issue.
I am also currently reading a very good National Academies Press book on the topic of sleep in teenagers which I intend to review soon, as well as use as a source for future rants on the topic.
Addendum: Alon Levy extends this discussion to the general issue of ageism as a conservative way to supress change by supressing the habringers of change – the next generation. Excellent read.
I’d like to go in a slightly different direction – the issue of Moral Order (scroll down to the “Adults Over Children” subheading). Of course, adults have moral authority over children. But what it means, i.e., how is this phrase understood and put to practice, differs between authoritarian/conservative and authoritative/liberal worldviews.
A conservative thinks about his child: “I am good and you are bad. I will beat the sh**t out of you for every little transgression and I hope that will teach you well. Learn to love the rod, because the discipline I am giving out today will turn into your self-discipline later. Once you are 18, get the hell out of my house – by that time you should be as moral as I am now.”
That is the recipe for the development of the External Locus of Moral Authority.
A liberal thinks about his child: “I am older, thus more educated, experienced and mature than you are. You are a good child and have a potential to become a deeply moral person. I am here to help you and guide you in solving day-to-day moral dilemmas so, by the time you are an adult, you will naturally strive to do good and behave ethically.”
That is the recipe for the development of the Internal Locus of Moral Authority.
The federal rules on pilot duty hours and rest periods aren’t the most comprehensible of reads.
One rule allows airlines to schedule pilots to fly for eight hours or less during a 24-hour period without a “rest period during those eight hours.” Another gives pilots who fly for more than eight hours in a 24-hour stretch a break of at least twice the number of hours flown, either “at or before the end of” the eight hours. Pilots who fly more than eight hours during a 24-hour period must receive 18 hours of rest before being assigned any other duties.
“Those rules underwent a modest updating in 1988,” Mazor said. “Then there was a proposal 10 years ago that was far from satisfactory to begin with, and we haven’t even gotten that.”
Mark Rosekind, a psychologist and president of Alertness Solutions in Cupertino, Calif., took part in that 1995 effort to rewrite the FAA flight crew duty and rest rules. At the time, he was a principal investigator with NASA’s Fatigue Countermeasures Program. Today, in addition to running his consulting company, he teaches a course on sleep, fatigue and circadian factors – the internal “clock” that affects numerous body functions – for the NTSB Academy in Ashburn, Va.
“Current FAA regulations were written in 1937 and have not been rewritten in any dramatic way since,” Rosekind said. “In 1937, jets didn’t exist. Today we have airplanes that have more range, travel into more time zones and do more short-haul routes. The regulations don’t reflect the industry today or changes in the science of sleep and circadian rhythms in 50 years.”
The FAA’s 1995 proposal called for a decrease in consecutive duty hours – which includes duties on the ground – from 16 to 14 hours, but an increase in maximum flying time to 10 hours during that 14-hour span. An FAA spokeswoman said the proposed rules drew more than 2,000 comments, mostly in opposition.
Light impacts human health and performance by enabling performance of visual tasks, controlling the body’s circadian system, affecting mood and perception, and by enabling critical chemical reactions in the body. Studies show that higher light levels are linked with better performance of complex visual tasks and light requirements increase with age.
By controlling the body’s circadian system, light impacts outcomes in healthcare settings by reducing depression among patients, decreasing length of stay in hospitals, improving sleep and circadian rhythm, lessening agitation among dementia patients, easing pain, and improving adjustment to night-shift work among staff.
The presence of windows in the workplace and access to daylight have been linked with increased satisfaction with the work environment. Further, exposure to light is critical for vitamin D metabolism in the human body. Light exposure also is used as a treatment for neonatal hyperbilirubinaemia.
Adequate and appropriate exposure to light is critical for health and well-being of patients as well as staff in healthcare settings. A combination of daylight and electric light can meet these needs.
Natural light should be incorporated into lighting design in healthcare settings, not only because it is beneficial to patients and staff, but also because it is light delivered at no cost and in a form that most people prefer.
Alfred Lewy and his colleagues in the OHSU Sleep and Mood Disorders Lab set out to test the hypothesis that circadian physiological rhythms become misaligned with the sleep/wake cycle during the short days of winter, causing some people to become depressed.
Usually these rhythms track to the later dawn in winter, resulting in a circadian phase delay with respect to sleep similar to what happens flying westward. Some people appear to be tracking to the earlier dusk of winter, causing a similar amount of misalignment but in the phase-advance direction. Symptom severity in patients with seasonal affective disorder correlated with the misalignment in either direction.
Recent research suggests that every cell in the body actually has its own clock–liver cells prepare for digestion at particular times of day; patterns of hormone production and brain activity exhibit cyclic peaks and valleys, says Siegelmann.
“The circadian system is really fundamental, it affects our behavior, our physiology and emotions,” she says. “The clock organizes the whole body into a very nice dance, and it organizes people together into a larger social orchestra.”
The so-called “local clocks” have natural circadian cycles that range from 21 to 26 hours, says Siegelmann. They are synchronized by the SCN, but the pathways and mechanisms by which this coordination happens aren’t fully understood. Evidence has recently emerged that the SCN itself is compartmentalized. One clump of cells responds to and processes information about light, they then alert an intermediate group of cells that transmit the information to more peripheral components.
This hierarchy within the circadian system introduces a time-delay in getting the entire body adjusted to a new environment, suggests Siegelmann. The delay is based, in part, on the strength of the connections between the different parts of the SCN, between the SCN and the peripheral clocks, and on the differing rhythms of the local clocks, she says.
To explore the dynamics of the system and how it responds to disruption Siegelmann and Leise designed a model with parameters reflecting this hierarchical nature. The model accounts for the SCN’s light-responsive component, its intermediate component, and the various peripheral components. It incorporates behavioral data, physiological data and what’s known about differences in natural circadian rhythms in the peripheral tissues. In rats, for example, internal organs such as the liver and lungs take a relatively long time to become synchronized with the SCN.
Simulations of the model revealed certain properties about both the stability and adaptability of the system, Siegelmann says. The light sensitive compartment of the master clock responds quickly, providing flexibility, whereas the intermediate compartment of the SCN seems to act as a buffer against small perturbations in the cycle.
The simulations suggest that the system gets most out of whack when the master clock is shifted forward between five and eight hours. After such a large leap, it appears that the master clock actually overshoots the desired time. Then, following a slight delay, the intermediate component and some of the peripheral components overshoot as well, depending on their inherent circadian time and their connectivity with the master clock. For example, the peripheral components that already tend to lag actually try to catch up by backtracking, achieving a leap forward of six hours by delaying themselves 18 hours.
You probably realize by now that my expertise is in clocks and calendars of birds, but blogging audience forces me to occasionally look into human clocks from a medical perspective. Reprinted below the fold are three old Circadiana posts about the connection between circadian clocks and the bipolar disorder, the third one being the longest and most involved. Here are the links to the original posts if you want to check the comments (especially the first comment on the third post):
January 18, 2005: Clocks and Bipolar Disorder
August 16, 2005: Bipolar? Avoid night shift
February 19, 2006: Lithium, Circadian Clocks and Bipolar Disorder
This list, written on December 17, 2005, is still quite up-to-date. There are also some more specialized books which are expensive, and many of those I’d like to have one day, but I cannot afford them (though I have placed a couple of them on my wish list, just in case I see a cheap copy come up for sale):
Truck drivers who routinely get too little sleep or suffer from sleep apnea show signs of fatigue and impaired performance that can make them a hazard on the road, according to a major new study by researchers at the University of Pennsylvania School of Medicine. The study results are published in the August 15th issue of the American Journal of Respiratory and Critical Care Medicine.
Different types of strokes occur most often at different times of day say scientists at Iwate Medical University in Iwate, Japan.
The team based their findings on data from 12,957 cases of first-ever stroke diagnosed by CT or MRI scans and drawn from the Iwate Stroke Registry between 1991 and 1996.The researchers chose patients who had experienced cerebral infarctions, or ischemic strokes, where cells die because blood flow to the brain is restricted, and two kinds of hemorrhagic strokes: intercerebral hemorrhages that occur within the brain, and subarachnoid hemorrhages that occur in arteries at the brain’s surface.
The wake-sleep cycle (circadian rhythm) was divided into 12 two-hour intervals. All three types of stroke had peaks between 6 and 8 in the morning and 6 and 8 in the evening with fewer incidents during sleep when blood pressure is the lowest. But cerebral infarctions had a higher peak in the morning and a lower peak in the afternoon and the two hemorrhagic strokes had a higher peak in the afternoon and a lower peak in the morning.
Wearing blue-blocking eyeglasses a few hours before bedtime resets the internal clocks to an earlier hour.
A novel way to advance the circadian cycle has been proposed as a way to solve the problem associated with the early starting times of middle and high schools. It has been recognized for some time that teen age students do not really wake up until well past the time they physically arrive at school. Researchers at Brown University have found that the student’s blood contains large amounts of the sleep hormone, melatonin. Researchers at the Lighting Innovations Institute of John Carroll University are seeking funding to carry out a study to find out if their method of advancing the melatonin cycle will help.
It is well known that exposing the eyes to light during the evening delays the start of the flow of melatonin until after the person has gone into the darkness of the bedroom. Because the students like to stay up late working on their computers or watching television, their melatonin cycle is delayed. This means that in the morning, the cycle doesn’t end until well after they are in school.
Five years ago it was discovered that not all light causes suppression of melatonin, only blue light. This means that wearing glasses that block blue light is the same as being in darkness as far as melatonin production is concerned. Putting on blue blocking glasses at 9:00 P.M. will move the circadian cycle forward in time so that the melatonin flow is over before the student gets to school.
The blue blocking glasses have been tested as a means to help people with sleeping problems. Putting on the glasses a few hours before bedtime allows melatonin to be present at the time people go to bed. This avoids the delay in falling asleep experienced by many people. Using the glasses also has been reported to help people sleep more soundly.
As a bonus, having melatonin present for a longer time may also reduce the risk of cancer. Melatonin is known to fight cancer in at least three ways. It is a powerful antioxidant, counteracting the damaging effects of free radicals produced by radiation and chemical pollutants. Melatonin also blunts the cancer-promoting nature of estrogen, and it interferes with the metabolism of materials that cancer cells require as food
Wearing the glasses in the late evening results in getting close to the conditions of light and dark experienced before the invention of artificial lighting. Glasses that block the damaging blue light are available at a web site of a spin-off company formed by the John Carroll researchers, http://www.lowbluelights.com. Filters for TV and computer screens as well as safe light bulbs are also available.
The John Carroll University researchers are seeking funding to test the glasses on high schools students to see if moving their circadian cycle forward in time will result in better academic performance in early morning classes.
Well, they are asking funding for research. The underlying science exists, so this is not total hogwash. And they are upfront about the business opportunities for themselves, selling the glasses already even before they did the research.
Today’s New York Times has a good article about jet-lag: The Science of Zzzzz’s. I am glad to hear that JetBlue is using scientific advice in helping their pilots be fresh and alert, especially now that JetBlue has started flying from RDU.
Oversimplified, but much believed idea: Many cancer drugs target cells during cell division. Healthy cells divide at a particular time of day (exact timing may differ between cell types). Cancer cells are not under the control of the circadian clock so they divide at all times of the day (and they divide more often anyway). Thus, incorrect timing of chemotherapy – given during the time most healthy cells divide as well as some cancer cells – will kill more healthy than cancerous cells, leading to early termination of treatment and worse prognosis. Correct timing – during the time when healthy cells are not dividing, but cancer cells are – will preferentially kill cancer cells, leading to a better outcome. That is the theory. Here is one example of a study testing this idea:
Chronomodulated Therapy for Colorectal Cancer Produces Promising Results in Men:
Among patients with metastatic colorectal cancer, administration of the chemotherapy drugs Eloxatin® (oxaliplatin), 5-fluorouracil, and leucovorin on a schedule that is adjusted to circadian rhythms (chronomodulated) appears to improve outcomes in men but not in women.
In an attempt to improve outcomes among patients treated with chemotherapy, researchers in Europe recently studied the effects of varying the delivery chemotherapy according to a patient’s circadian rhythm (the body’s 24-hour cycle). The idea behind this approach is that there may be certain points in the circadian rhythm when chemotherapy drugs will have the greatest effect with the least toxicity. Varying delivery of treatment according to the circadian rhythm is referred to as chronomodulated therapy.
* Overall, survival was similar in the two treatment groups: Among patients treated with FOLFOX2, 36.9% of patients survived for two years or longer. Among patients treated with chronoFLO4, 37% of patients survived for two years or longer.
* The frequency of serious side effects was similar in the two treatment groups, but the types of side effects varied. Patients treated with FOLFOX2 were more likely to experience low white blood cell counts (neutropenia), and patients treated with chronoFLO4 were more likely to experience problems such as diarrhea.
* The effect of chronoFLO4 differed by sex. Among men, those treated with chronoFLO4 had a 25% reduction in risk of death compared to those treated with FOLFOX2. Among women, those treated with chronoFLO4 had a 38% increase in risk of death compared to those treated with FOLFOX2. The reasons for this difference between men and women are uncertain.
I really need to get back in the saddle and continue studying sex differences in circadian function….
Patients who undergo surgery late in the afternoon are more likely to experience unexpected adverse events related to their anesthesia than are patients whose operations begin in the morning, a new analysis by Duke University Medical Center researchers suggests.
In addition to spotting problems related to anesthesia, Wright and her colleagues also found that surgery patients experienced a significant increase in “administrative delays” during late afternoon, which might contribute to the increase in adverse events that occur during this time. The delays included waiting for laboratory test results, doctors running late, transporters not being available to move patients and rooms not being ready on time.
Based on their findings, Wright and her colleagues suggest a number of factors that might contribute to variations in health outcomes. These factors include fatigue among health care providers, swings in the circadian rhythms that influence a person’s natural ups and downs over the course of a day, and institutional work schedules.
Wright said that many factors, involving both patients and hospitals, may contribute to increased rates of adverse events late in the afternoon. For example, patients may be more susceptible to either pain or post operative nausea and vomiting in the late afternoon. We don’t know if issues such as not having eaten all day or spending a stressful day waiting in the hospital may have an influence on this, Wright said.
Late afternoon also is a time when changes in the teams that administer anesthesia during surgery coincide with natural circadian rhythm lows, Wright said. The circadian rhythm serves as the body’s internal clock that regulates sleep, brain wave activity and other bodily functions. Circadian lows occurring around 3 p.m. to 5 p.m. and again at 3 a.m. to 5 a.m may affect human performance of complex tasks such as those required in anesthesia care. Changes in anesthesia care teams usually occur around 7 am and again between 4 pm and 6 pm. End of day fatigue, a circadian low point, and changes in care team are all occurring around 3 pm to 6 pm and may be interacting in a way that affects patient care, she said.
This was know before, but the size and scope of this study is remarkable.
Half the people in modern urban societies suffer from “social jet lag” because their body clocks are seriously out of step with their real lives, the Euroscience forum in Munich heard on Monday.
The result was chronic fatigue and an increased susceptibility to disease, researches found. They concluded that employers should tell staff to wake up in their own time and come in to work when they feel ready to.
Till Roenneberg, a circadian rhythm researcher at Ludwig Maximilians University in Munich, coined the phrase “social jet lag” after a survey of 40,000 people in Germany and Austria – and a more detailed follow-up study of 500 – showed a persistent mismatch of at least two hours between their biological clocks and the demands of their jobs or education.
One striking research finding was that people suffering from social jet lag were much more likely to smoke. “Among those who had no social jet lag, 10 per cent smoked; at two hours the proportion was up to 30 per cent and at four hours we found 60 per cent smoked.”
Employers and schools could do a lot to help, by adjusting their working hours, said Martha Merrow of Groningen University in the Netherlands. “Schools should open later; I think 10am would be sensible but no one wants the inconvenience of making the change.”
According to Prof Roenneberg, “those people who suffer the least social jet lag are late types who can choose their own working times. Employers should say: ‘Please wake up in your own time and come in when you are ready.'”
Computer-mediated work and networks, which bring groups together on radically different schedules than the 19th and 20th centuries’ work habits. We have an opportunity to rethink the organization of work. Should we start with recognizing schedules in shared workspaces need to be more flexible? I think so, especially when you consider that more work can be done at home, allowing people to spend time with their families and contribute to the raising of the next generation while continuing intense professional engagement with the economic world.
I did not find it surprising. If you have money, you can buy yourself time – to exercise, to eat a good meal at a nice restaurant or to fix healthy food at home, and to sleep as much as your body needs. As a result, you will be healthier overall. You can read about the study here (hat-tip:Sleepdoctor)
This week, it took me quite a while to figure out how to answer the Ask a ScienceBlogger question: “What are some unsung successes that have occurred as a result of using science to guide policy?”
As a relative newcomer to the United States, and even more a newcomer to American politics, I was not around long enough to pay attention to various science-driven policies of the past. Most of what I know are far from “unsung” successes – from Manhattan Project, through Clean Air and Clean Water acts, to the EWndangered Species Act, to the international Kyoto Protocol. Dealing with DDT, DES, thalidomide is also well-known. The space program is quite well sung! Various policies in other countries are also well known at least to the local population.
So, I thought, I should probably take a look at some issues that, informed by science, became policy at the state or local level. Then, my wife reminded me about the topic I know something about, as I have written about it several times before, e.g., here, here and here.
That’s right. Forward-looking school systems in reality-based communities around the country have, over the last several years, implemented a policy that is based on science – sending elementary school kids to school first in the morning, middle-schoolers next, and high-schooler last. This is based on the effects of puberty on the performance of the human circadian clock. For teenagers, 6am is practically midnight – their bodies have barely begun to sleep. Although there have been some irrational (or on-the-surface-economics-based) voices of opposition – based on conservative notions of laziness – they were not reasonable enough, especially not in comparison to the scientific and medical information at hand, for school boards to reject these changes.
So, click on the links above for my long-winded rants on the topic, both the science part and the policy part. I am very happy that my kids are going to school in such an enlightened environment, and I am also happy to note that every year more school systems adopt the reasonable starting schedules based on current scientific knowledge.
The absence of light-dark cycles in space (e.g., on the shuttle or space station) results in disruptions of sleep. It has been proposed that humans who spend prolonged time in space are suffering from jet-lag – the internal desynchronization of clocks in various tissues.
A new experiment on the space station will take a somewhat different strategy than usual. Instead of measuring EEG (brain activity), it will monitor EKG (heart activity) over a period of 150 days.
The idea, brought by Irish researchers, is that EEG monitoring is not capable of measuring internal desynchronization of the myriads of clocks in our body. If the astronauts are indeed jet-lagged, this may not be apparent from the measurement of brain function which presumably follows the timing of the main pacemaker in the suprachiasmatic nucleus. The new approach will also look at the timing of peripheral oscillators to see if they are out of sync with the brain – which would be the true marker of jet-lag.
Rozerem is a selective melatonin agonist. It acts on melatonin receptors at the suprachiasmatic nucleus. It is prescribed as a non-addictive sleep aid for people having difficulties with the onset of sleep, i.e., falling asleep in the evening.
While melatonin itself appears unlikely to be a molecule that directly induces sleep, it does have phase-resetting effects on the circadian clock. Thus, Rozerem appears ideal as an aid for extreme “owls” to help them fall asleep (if they need to wake up early in the morning, as some jobs require). By mimicking melatonin, it would phase-advance the clock by a couple of hours and make it easier to fall asleep at a more socially acceptable time.
I did not really spend much time thinking about this, but my wife just told me something interesting. Last night, she took Rozerem and fell asleep practically instantly and had a great night of sleep. But, last week, when she tried using Rozerem in the morning after coming back home from her 12-hour night shift, there was no effect.
Perhaps Rozerem, just like melatonin, is incapable of inducing instant 12-hour phase-shifts of the circadian clock in the SCN. Shifting by a couple of hours is fine, but shifting the cycle by 180 degrees is a different story altogether – it may take several days to accomplish.
Perhaps the clock in the SCN has its own Phase-Response Curve (PRC) to melatonin – presence of the molecule induces smaller or bigger (or not at all) phase-advances or phase-delays depending on the phase of the cycle in which it is applied.
So, perhaps Rozerem given in the evening hits the PRC at the phase in which a large (i.e., 2-3 hours) phase-advance is induced, thus placing the body at the right time for the onset of sleep. By the same logic, application of Rozerem in the morning may hit the PRC at the phase in which it has no effect or an effect in the wrong direction – phase-advance again, which would bring the body at the proper time for brunch! I guess I’ll need to dig through the old literature on the melatonin PRCs in humans to see how it looks like and if this notion may be correct.
Perhaps if one works a night shift and repeatedly applies Rozerem every morning, there would be a gradual shift of the clock, over several days, until the correct phase is achieved at which the drug would work as advertised. Also, avoiding any conflicting cues to the clock (e.g., light, noise, etc.) would seem important to ensure that a morning dose of Rozerem has its intended effect for night-shift workers. All of this is late-night speculation, though, so do not take my word for it. It is based on a single data-point. More research is needed….
MILAN, Italy, June 16 (UPI) — Scientists in Italy say they have discovered that the grapes used in popular red wines may contain high levels of the sleep hormone melatonin.
Melatonin is naturally secreted by the pineal gland in the brain, especially at night, and it tells the body when it is time to sleep, according to researcher Iriti Marcello at the University of Milan.
Hey, hey, what do you say:
Until recently, melatonin was thought to be exclusively produced by mammals, but has recently been discovered in plants.
Excuse me, but we’ve known for decades that melatonin is produced by all vertebrates, many, many invertebrates, some protists (including sea kelp), and, yes many plants. Bananas are famous for their high melatonin content.
Iriti’s study, published in the Journal of the Science of Food and Agriculture, discovered high levels of melatonin in Nebbolo, Merlot, Cabernet Savignon, Sangiovesse and Croatina grape varieties.
“The melatonin content in wine could help regulate the circadian rhythm — sleep-wake patterns — just like the melatonin produced by the pineal gland in mammals,” says Marcello.
However, Richard Wurtman of the Massachusetts Institute of Technology, says he is unconvinced and believes further research is needed to determine whether the compounds discovered are melatonin — or something very similar.
Wonder why Wurtman said this? I’d need to look at the paper – why is it considered to be iffy. Melatonin assays are pain in the behind to do, but they work.
Anyone, whatever benefits melatonin may have to put one to sleep in the evening probably require imbibing vast quantities of wine which also contains alcohol which fragments sleep (or eating a few pounds of grapes not selected for table use) – thus countering the effects of melatonin. Cute idea, anyway.
So, Wellbutrin is now officially a drug for treating Seasonal Affective Disorder. And chocolate is so unofficially. But, those may only take the edge off of the symptoms – they cannot affect the underlying causes.
This post is perhaps not my best post, but is, by far, my most popular ever. Sick and tired of politics after the 2004 election I decided to start a science-only blog – Circadiana. After a couple of days of fiddling with the templae, on January 8, 2005, I posted the very first post, this one, at 2:53 AM and went to bed. When I woke up I was astonished as the Sitemeter was going wild! This post was linked by BoingBoing and later that day, by Andrew Sullivan. It has been linked by people ever since, as recently as a couple of days ago, although the post is a year and a half old. Interestingly, it is not linked so much by science or medical bloggers, but much more by people who write about gizmos and gadgets or popular culture on LiveJournal, Xanga and MySpace, as well as people putting the link on their del.icio.us and stumbleupon lists. In order to redirect traffic away from Circadiana and to here, I am reposting it today, under the fold.
Update: This post is now on Digg and Totalfark. I urge the new readers to look around the site – just click on the little SB logo in the upper left corner. Also, several points made briefly in this post are elaborated further over on Circadiana, as well as here – just browse my Sleep category.