ClockQuotes (Prudden)

You can't turn back the clock, but you can wind it up again.
- Bonnie Prudden

After the Grand Rounds

Apart from getting a 1000 hits per day (about half from Instapundit, the other half mostly from combined efforts of Pharyngula and Majikthise and a few hits from all the others), hosting Grand Rounds had additional benefits, namely discovering some new interesting bloggers.

For instance, a visitor alerted me to an interesting sleep case:

"A 2000 account on the Kleine-Levin Syndrome Foundation web site tells of S, who had night terrors as a child and then multiple episodes of excessive sleep beginning when he was 14 years old."

A new blog I discovered via the Instalanche is Emergiblog, a brand new blog by a nurse in California. There are only a few posts so far but they are exceptionally well written and fun to read. Of course, the post titled Circadian Rhythm Caper is really the coolest to me....

Grand Rounds #47 - From one room to another

I'd like to welcome you all to Grand Rounds, the blog carnival of all things medical.

I have hosted a dozen carnivals so far, I am very interested in the concept of the blog carnival, and I compile a monthly Meta-Carnival, so it's strange that I have not hosted Grand Rounds before.

This may be because I am not an MD or an RN (though my wife is). I am not even a PhD yet (though this will change in a couple of months). Still, this blog (and I sure hope you take some time to look around) is dedicated to the science of chronobiology and the medicine of sleep (I am aware of only two other bloggers who are in the field - any others for the blogroll?), and I leave posts about personal life, blog memes, books/movies, current events and my political rants out of here (on my other blog) so, heck, why not invite a bunch of health professionals over here for some cool med-blogging.

Of all the carnivals out there, Grand Rounds tends to have some of the most creative hosts (to be fair, Skeptic's Circle and The Tar Heel Tavern had some very creative hosts, too) and I have done some creative thematic carnivals in the past, but for today I decided to "play it safe" and just present a simple introduction to medical bloggers and their best recent posts, organized by Rooms - the places where stuff is happening. So, let's do it!

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In the Classroom

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Let's start with a good laugh. The Drunken Lagomorph reminisces about an important moment in anyone's personal history: How I learned the difference between farts and boners.

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From the Clinical Cases and Images Blog a link to an excellent teaching and reference resource: 30,000 Medical Images, Tables and Figures from Leading Textbooks are Online.

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In the Emergency Room

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It is apparently not unheard of for a woman to give birth without experiencing the wonder and joy of pregnancy. Mike Pechar of Interested-Participant may himself have been an interested participant in a pregnancy or two, but it is rare to hear about an example of Birth Without Pregnancy.

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DrTony woke up the squimishness in me with a post about, among else, hanging.

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In the Ambulance (not a Room)

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From Lingual Nerve a breath-taking (or breathless) story:
Not Breathing.
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In the Hospital Room

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From Keith of the Digital Doorway a saga from the frontline of nursing in two parts: The Language of Illness and Stories Unfolding.

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Tony writes on the Hospital Impact blog. This post is on the unique issues faced by male nurses.

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Maria of Intueri wrote An Open Letter to All the Patients I Have Ever Cared For: "It is an expression of my appreciation for all the people who have put their faith (sometimes I wonder blindly) in me as their medical student or doctor."

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From Over My Med Body a thought about a patient, and patients in general...as people, not diseases: The Patient Snapshot.

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From Time To Lean - it's not easy being a nurse: Injury report.

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Outdoors (by definition not a Room)

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From Mr. Hassle's Long Underpants an exercise in Field Orthopedics:
If it's bent, straighten it

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Dr Emer of Parallel Universes sent: Walk! "With the rising oil prices, Filipino citizens are asked by their President to walk or use bicycles." A silver lining?

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From my other blog Science And Politics a post about a study performed outdoors and why that matters: Malaria and Melatonin: Co-evolution Around The Circadian Clock

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On the Internets and beyond (each in own Room, sometimes padded)

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Orac of Respectful Insolence keeps fighting the "alties" and exposes their tactics and rhetorics in The pharma shill gambit.

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Alun from Archaeoastronomy has an entry on Dr Chris Malyszewicz:
Let’s hear it for Dr Chris Malyszewicz. He's someone who wants to sell a magic bullet for MRSA. So what he does is give the national papers in the UK stories about how MRSA levels in various places are 40 times higher than the 'safe level'. When he hits a hospital they do their own checks and find no MRSA and it seems Malyszewicz doesn't keep his samples, but that doesn't help with the inevitable bad publicity.

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In the Doctor's Office (also a Room)

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From Majikthise: Pediatricians and obesity: "A recent survey of 738 North Carolina pediatricians found that self-described thin docs are reluctant to counsel their patients about obesity compared to their heavier colleagues."

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From The Examining Room of Dr. Charles a great story: Cutting Beauty.

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DB of DB's Medical Rants wrote What this patient needs is a doctor! Sure, an old saying, but DB is using it in a very different sense.

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From Shrinkette a look at the labyrinth the patients need to wade through:
A Lonely, Uncertain Road.

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Rare tumors, empowered patients, long trips for expert care is an essay on the changing doctor/patient relationship, from Kent of Sound Practice.

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In the Science Lab (a Room, too)

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Amy of Diabetes Mine on The Great Glycemic Index Debate and how iffy it is.

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From Dr.Lei of Genetics and Public Health Blog on the utility of genetic information at this early stage of the genomic revolution: What's the Point of Finding Genes?

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From KidneyNotes: Tandem Heart is a percutaneous ventricular assist device placed by cardiologists.

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Michelle is The Krafty Librarian.
Flaws in Validating Medical Studies. An article in the Boston Globe and in PLoS question the validity of many published medical research articles. The entire peer review process is questioned. According to the PLoS article, "It can be proven that most claimed research findings are false." Where does that leave us, who depend on research to treat or be treated?

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I wrote a short post on Circadiana about relationship between circadian rhythms and the bipolar disorder: Bipolar - Avoid night shift.

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In the Hospital Boardroom

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Sumer Sethi of Sumer's Radiology Site sent IMAGING REFFERAL-A revolutionary concept for the radiologists in India. Who is actually making a diagnosis?

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Allen of Gruntdoc sends Doctors push St. Luke's to forgo $25 million gift. He says: "Why a hospital would take a plaintiff attorney's money and then put his name
on a hospital tower is utterly beyond me. I am not alone."

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Aggravated DocSurg in EMTALA, ED Call, and Medicare writes: "...many specialists (and non-specialists) view ED coverage as a poorly reimbursed burden, laden with a worrisome risk for malpractice exposure. On the other hand, hospitals need to have specialty coverage commensurate with the services they provide for elective patients..."

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From The Nurse Practitioner's Place: Hospital Acquired Infections - Report or Not?
"If you try to hide information that could be potentially important to patients, it could be perceived as suspicious."

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Dr Bob from The Doctor Is In: Quality in Medicine - Part 2: Transparency, the second part of an ongoing series on assuring quality in health care, this post addresses some ideas on improving transparency in medicine.

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In the smoke-filled backroom (of newspapers or Congress)

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InsureBlog on genetic testing in the workplace: Wearing Genes to Work.... While it's still somewhat "under the radar," it's a topic of interest.

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From the HealthyConcerns dot com blog a sharp look at a poll with leading questions: More on wages vs. health benefits: "Polls about what employees want (pay raises or health benefits) come up with contradictory results, but it may be all in how they asked the questions".

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This week on the Health Care blog, Matthew Holt wonders if recent moves to expand state Medicaid programs could ultimately lead to universal insurance.

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Here, a post from theHealth Business Blog puts a political spin on some worrysome statistics: Motorcyclists: Libertarians or Socialists?

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From Red State Moron a post regarding a recent editorial in the New York Times on “Workaholism and Obstetrics”.

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Now, after all this HTML typing I need you docs to tell me how to fix my carpal tunnel!

Please go and dig through the archives of Grand Rounds and check the submission guidelines so you can send your entries for next week to Straight From The Doc.

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Addendum: I'd like to thank all who have contributed to the carnival, as well as all who have posted a link to it (if I missed you - let me know, as it is hard to discover all the links amid the Instalanche): Pharyngula, Majikthise, Drunken Lagomorph, Respectful Insolence, Archaeastronomy, Blogborygmi, Dr.Charles, Cut To Cure, Science And Politics, Medpundit, CodeBlog, Gruntdoc, Medmusings, KevinMD, Kidney Notes, Dr.Tony, DB's Medical Rants, Gamecockdoc, Braised Lambchop, Accidental Verbosity, Nurse Practicioner's Place, Jayne Doodles, Straightfromthedoc, MSSP Nexus Blog, Digital Doorway, Parallel Universes, Genetics and Public Health Blog, DocSurg, Insure Blog, HealthyConcerns.com, Health Business Blog, Dean's World, Red State Moron, TTLB Ubercarnival and Instapundit.

Bipolar? Avoid night shift.

I have only touched a little bit on the topic of interaction between the circadian clock and Bipolar Disorder before. You can find stuff online like this, this and this.

What I'd like to focus on right now is an interesting hypothesis, called the Social Rhythm Stability Hypothesis (SRSH). One of the originators of this hypothesis is Cindy Ehlers, now at Scripps (See her website here. See one of her papers, e.g,. Ehlers CL, Kupfer DJ, Frank E, Monk TH. Biological rhythms and depression: The role of Zeitgebers and zeitstorers. Depression 1:285-293, 1994.).

According to SRSH, the core problem in bipolar disorder is instability of regular daily patterns of activity. As I have mentioned before, light-dark cycle is the most powerful environmental cue (Zeitgeber) that entrains circadian rhythms, but is not the only one. Cold-blooded animals entrain to temperature cycles, and several other cues have been demonstrated in various species. Humans are extremely sensitive to social cues. Getting a brief social cue about time of day resets the human clock even if all other cues (e.g., light) are removed.

Social rhythms in bipolar patients remain stable if the social Zeitgebers are stable. People around you have their own regular schedules, both at work and at home. Your pets ask to be walked on the leash at exactly the same time each day. This is good.

What is bad is that bipolar patients are extremely sensitive to disruptions of social schedules. Ehlers and others coined a new term - Zeitstorer - to describe a person or a social demand that throws off the regularity of the daily pattern of activity. Whenever you start a new relationship, get a new job, buy a new pet, or have a baby, your schedule is disrupted. If you are bipolar, this will result in wild cycling until you get used to the new routine.

Now consider getting a job that demands you work on a rotating shift. You are getting a Zeitstorer every week! Bad idea if you are a bipolar sufferer. Even a steady night shift is a disturbance as such a pattern in hard on one's body and one also tends to shift back to daytime activities over the weekends.

Is SRSH a realistic hypothesis? I say - why not? It has been shown long ago that circadian rhythm disturbances are both causes and symptoms of bipolar disorder. During depressive episodes, the phase is advanced - you usually become more of a "lark", you wake up earlier and have a lesser total amount of activity per day. During manic episodes, one is more of an "owl", staying up late and increasing total daily activity.

Lithium is one of the rare chemicals that has been shown to affect the period of the circadian clock. For instance you can see here that even individual neurons of the mammalian clock (the SCN) lengthen their period when exposed to lithium. If you have paid attention in class you know that period determines phase. Increasing the period delays the phase (if your period is 25 hours you will wake up 1 hour after dawn every day, if your period is 23 hours you will wake up 1 hour before dawn every day - that works in humans only if you exit civilization and live out in the wild). Thus lithium phase-delays the rhythm which is already phase-advanced, thus, hopefully, putting back into a normal phase.

Photoperiodism - Models and Experimental Approaches

In the previous ClockTutorials post, I wrote about the adaptive function of seasonality. Here, I will focus on photoperiodic time measurement - mostly on conceptual models and experimental designs invented to test those models. In the next installment, I will concentrate on actual physiology of photoperiodism, particularly in mammals, and then apply that to the human affliction - the Seasonal Affective Disorder (SAD, or 'Winter Blues').

Timely prediction of seasonal periods of weather conditions, food availability or predator activity is crucial for survival of many species. Although not the only parameter, the changing length of the photoperiod ('daylength') is the most predictive environmental cue for the seasonal timing of physiology and behavior, most notably for timing of migration, hibernation and reproduction. While rising spring temperatures may vary from year to year, the gradual increase in daylength is uniform and precise. Still, some cold-blooded organisms also respond to thermoperiod (oscillations between increasing duration of warmth during the days and decreasing duration of cold temperature during the nights) and some modulate their photoperiodic response by overall temperature levels.

Models of Photoperiodism

Three main models for photoperiodic time measurement have been proposed.

Garner and Allard, in 1920, discovered photoperiodism in plants. Soon afterwards, they and other researchers confirmed that changes in daylength, in absence of any other clues, trigger flowering in a number of plant species. Some respond to lengthening days in the spring, others to shortening days of the fall. Similar findings in insects, mammals and birds soon followed. The way these early researchers conceptualized photoperiodic response was later named the "hourglass model".

The hourglass model assumes the gradual accumulation of a chemical product in the organism. A certain quantity of this chemical is necessary to trigger a physiological response (e.g., flowering in plants, or growth of gonads in mammals). The threshold is reached if the product is not first degraded. It may be degraded by dark and only accumulates during the light phase or it may accumulate during dark and be degraded by light. If the light (or the dark) is long enough threshold is reached and a physiological response, such as maturation of the reproductive system, is initiated. This model argues against the involvement of the circadian clock in the photoperiodic response because the hourglass lacks endogenous rhythmicity and must be reset or "turned over" by the light cycle each day:

The involvement of the circadian system was, however, detected in almost all species studied to date, so the hourglass mechanism is unlikely to have evolved in real organisms. However, its historical primacy, its simplicity which appeals to our sense of parsimony, and its usefulness as a hypothesis to test against, make the hourglass model an integral part of the scientific repertoire in the study of photoperiodism.

The external coincidence model was proposed by one of the pioneers of chronobiology, Erwin Bunning, in 1936. This model proposed the existence of a circadian rhythm of photoperiodic photosensitivity (CRPP) in which most of the night-phase is sensitive to light, while the day-phase is photoinsensitive. As the day gets longer in spring, light starts illuminating the photosensitive phase and triggers the physiological or behavioral response:

In this model light has a dual effect: it entrains the rhythm of photosensitivity and also acts as the stimulus (that is stimulates a photoperiodic response) if the light falls on a photosensitive phase of the rhythm of photoperiodic sensitivity. This model is termed an "external coincidence" model because it requires the coincidence (hatched red) of an external stimulus (light) with an internal rhythm of sensitivity to light.

This dual role of light is not necessary if one considers the "internal coincidence" model, proposed by Colin Pittendrigh and Dorothea Minis in 1964. In this model, the light's only role is to entrain the circadian system. At the time this model was proposed, it was becoming apparent that multicellular organisms house more than one circadian pacemaker. Each of the oscillators will behave differently under the influence of the light-dark cycles, and assume different phase-relationships with the entraining cycle.

Pittendrigh and Minis proposed that changing photoperiods may alter the internal phase-relationships between two or more rhythms, bringing them into permissive (red) or inhibitory modes. For example, secretion of a hormone has to coincide with the availability of its receptors at the target tissue, or with the absence of the enzyme that metabolizes it. In this model, therefore, light must control only the internal phase-relationships between multiple circadian rhythms:
Experimental Evidence

Several experimental protocols have been developed to test circadian involvement in the photoperiodic response. Positive results of these experiments eliminate the hourglass model, thus confirm the involvement of the circadian system in photoperiodic time measurement. It was always hoped that, in the process, these experiments would also be able to distinguish between the internal and external coincidence models.

These protocols involve the use of night-break light pulses (i.e., skeleton photoperiods, see the "Entrainment" series of posts), resonance light cycles, and non-24 hour cycles ("T-cycle experiment") of light and dark.

Skeleton photoperiods mimic the full photoperiods with the light pulses at the times of dawn and dusk only. Although the total time per day that the animal spends in light is quite small, the photoperiodic response is elicited if the night-break pulse (or the second of the two skeleton pulses) falls during the photoinductive phase of the circadian cycle.

However, in skeleton photoperiods, it is often impossible to mimic long photoperiods as the circadian system tends to entrain to the shorter of the two possible interpretations of the skeleton photoperiods. Also, there is often an additional complication of phase-shifting effects of both pulses.

Resonance cycles are light-dark regimes in which the period T (L+D) is a multiple of 12 hours (e.g., LD 6:18, LD 6:30, LD 6:42, LD 6:54, etc.). If the circadian system is involved, every other light pulse will fall onto the photosensitive phase and induce a photoperiodic response in all cycles which are odd multiples of 12 hours (e.g., LD6:18, LD 6:42), while in cycles which are even multiples of 12 hours (e.g., LD 6:30, LD 6:54) the photoperiodic response will not be seen because every light pulse falls only during the insensitive phase of the rhythm of photoperiodic photosensitivity. In resonance cycles, the long periods of darkness may theoretically counter the stimulatory effects of the rare light pulses.

In T-cycle experiments, the period (T) of the LD cycle is different from 24 hours and varies within the limits of entrainment. During entrainment, the phase of the pacemaker is shifted or reset each cycle by an amount (Df) equal to the difference between the freerunning period (t) and the period (T) of the entraining cycle ( t - T = Df). The phase angle (y) between the onset of light and the onset of circadian activity will be characteristic of each T-cycle and can be calculated from the phase-response curve (PRC).

The PRC describes the phase-shifting behavior (lengths of advances or delays) of a circadian system elicited by a specific environmental perturbation (e.g., a pulse of light of defined length, intensity and wavelength) as a function of circadian timing of that perturbation. As a general rule, light pulses given around early subjective night elicit phase-delays, while those given late in the subjective night result in phase-advances.

In LD cycles of different period lengths, the phase angles between the onset of circadian activity and the onset of the light phase of the cycle will be different and predictable from the PRC. Accordingly, on some T-cycles the circadian system will be entrained in such a way that the light pulse illuminates a portion of the photoinducible phase (fi) and result in a measurable physiological photoperiodic response. If the internal coincidence model is correct, the entraining LD cycle will control the phases of different circadian outputs differently, thus changing the phase relationships between two or more circadian rhythms within the organism. Light-dark cycles of certain period lengths (T) will then bring the relevant rhythms into a phase relationship that results in the stimulation of the photoperiodically controlled physiological system.

The T-cycle protocol does not have the same difficulties in interpretation as the other two protocols. Only one light pulse per cycle is used and it has both an entraining and a potential photostimulatory effect. Utilizing different period-length cycles spanning the limits of entrainment of the organism, the light pulse can be brought into every possible phase-relationship with the circadian system. As the animals assume stable entrainment, the light pulse and the circadian system will assume a different phase-angle in each T-cycle. Presumably, in some of the cycles the light will repeatedly illuminate the photoperiodically photosensitive phase leading to the physiological response, while in other T-cycles, the light will be coincident only with the subjective day, leading to the lack of stimulation.

If an internal coincidence mechanism is operating, it is likely that the T-cycles will place the two circadian oscillators in all possible phase-relationships, leading to the stimulation in some and inhibition of response in other values of T. In theory, the two models may have different predictions as to which Ts will be inductive and which not.

So, what's the evidence?

In many organisms short days inhibit while long days stimulate various seasonal responses of physiology and behavior. Various experimental paradigms, including skeleton photoperiods and resonance cycles, demonstrated that it is not the total amount of light, but the precise temporal placing of the light that induces the photoperiodic response, giving the circadian system a role in the measurement and interpretation of daylength.

In a large number of species, including both invertebrates and vertebrates, as well as plants, these protocols have proven the involvement of the circadian system in photoperiodic time measurement, e.g., resonance cycles in male rosefinches, skeleton photoperiods in the rain quail Coturnix coromendelica, T-cycles and resonance cycles in golden hamsters and house finches, etc.

On the other hand, there are some organisms in which the results of all these protocols are not so conclusive. For instance, T-cycle and night-break studies in blackheaded buntings indicate the dependence of the reproductive response on the period (T) of the cycle and on the length of the light pulse within the cycle. In starlings, effects of light intensity, wavelength and pulse length can be seen even in 24 hour cycles.

Although the involvement of the circadian system has been documented in many species, it has not yet been possible to discriminate between the external and the internal coincidence mechanism for photoperiodic time measurement. So far, results of skeleton photoperiod, resonance cycle and T-cycle experiments could be interpreted equally well with both models.

Moreover, in some species it was even difficult to differentiate between the hourglass and circadian models. The vetch aphid (Megoura viciae) is probably the most notorious example. A mathematical model, though, was developed that succesfully describes photoperiodic responses in all of the hundreds of arthropod species that were studied over the past century. The fact that this mathematical model is consistent with all the experimental data on the vetch aphid suggests that it may also use its circadian clock to measure photoperiod, it's just that its clock's putput is of a very small amplitude.

Another species that was difficult to figure out was American chameleon (Anolis carolinensis). Initial studies suggested that hourglass model was operating. However, later work by Linda Hyde utilizing T-cycles showed that the circadian clock is indeed involved in photoperiodic time measurement in this species.

Finally, in Japanese quail (Coturnix japonica), results of skeleton photoperiods were positive, resonance cycles suggest some involvement of the clock but not the complete response, and the T-cycles were negative. This is also a species with a low-amplitude circadian system (i.e., it has a Type 0 PRC), so it is likely that clock is involved but the final demonstration is still waiting for the next creative experimenter to provide.

Category: Clock Tutorials

ClockQuotes (Häfiz)

Our brains are seventy-year clocks. The Angel of Life winds them up once for all, then closes the case, and gives the key into the hand of the Angel of the Resurrection. - Häfiz

Life would be easier if money was never invented...

Darn, my wife got paid yesterday and we paid the neccessary bills, those that will prevent the imminent cutting off of water, power, phone and Internet access and repossession of the car. One trip to the grocery store later and today our balance in the bank (both checking and savings) is zero. I don't get to teach until October. The restaurant up the street assured me they would hire me but, so far, no call from them. Next paycheck goes for rent. And nobody hit the PayPal button in almost two months....

ClockNews #33

Lag Drag

As motivational speaker and humorist Linda Perret once said, "Jet lag is nature's way of making you look like your passport photo."

Nighttime risk for newborns

While the superstitious might attribute the difference to astrology, numerology or perhaps even circadian rhythms, Gould said hospitals are the primary suspects. "There may be some hospitals that are really stressed at night in being able to meet patients' needs," he said.

Stuff dreams are made of

The National Institutes of Health have identified teens and young adults 12 to 25 as a population at high risk for problem sleepiness. In addition to poor performance at work or school, sleepiness leads to injuries and deaths from accidents. Drivers under 25 are involved in more than half of all fall-asleep crashes. Sleep deprivation also is linked to depression and might be a factor in attention deficit disorder.

That Morning Workout Could Be Fatal

Early morning joggers, swimmers and fitness fanatics who use the gym before breakfast are putting themselves at greater risk of infections than evening exercisers, scientists now claim.

Sex-based physiology prior to political correctness

Readers of this classic paper will immediately notice differences in the structure of that paper compared with reports of today. One obvious difference between the two groups of papers separated by almost half a century is the minimalistic statistical analysis of the data. Unlike requirements for some journals today for "independent statistical review," statistics of the Critchlow study were described with one sentence: "All statistical probabilities were derived from analysis of variance." Figures and text, unlike today's papers, were not peppered with the prerequisite asterisks, crosses, and P values to the nth decimal level of statistical significance. Differences between responses of male and female animals are obvious to the reader and as such emphasize that statistics are a tool, like other scientific assays, and statistical significance should not override common sense.

A second difference between papers of today and the Critchlow study is the lack of translational relevance or applied rationale for the study. In a recent interview with Dr. Critchlow, he indicated that his group simply needed reliable baseline information from which to design future experiments. Although their investigative team had considered possible clinical relevance of their observations, he and his colleagues were simply not aware of any. Needless to say, observations from these basic experiments have clinical relevance today. Indeed, it has taken over 40 years for sexual dimorphic responses to cortisol to be observed and validated in pubertal humans (10), and today it is recognized that estrogen-modulated release of ACTH has implications for sex disparities in incidence of depression, reproductive disorders (4), and perhaps acute stress-induced Tako-Tsubo cardiopathy (1).

By today's standards, the study by Critchlow and colleagues could perhaps be labeled "descriptive," an adjective that often pronounces a death sentence for publication of papers in so-called "high-impact" journals. Fortunately, physiologists recognize the value of definitive, descriptive, integrative experiments that provide insight into controversial findings. It is just such descriptive observations that are still cited after 40 years (9) because they provide the background information that is necessary to explore more mechanistic approaches to understanding how physiological systems are modulated.

In the Dark

Night-shift workers can feel isolated, hostile -- and just plain tired

It's when you don't snooze that you can lose

Failing to get the proper amount of sleep can raise the risk of serious health problems and experts often recommend getting eight hours each night. But the exact amount of sleep you need depends on many factors.

We're only human, none of us made to run like machines

It's hard to believe that not long ago, most people actually went to bed when the sun went down and got up when the sun came up.

Sleepless nights may cause ulcer

Researchers in the UK have discovered that the protein TFF2, which aids in stomach lining repair, mostly acts during the night when we sleep.

Faulty Biological Clocks May Influence Addiction

A gene that regulates the body's circadian rhythms, including sleep and wakefulness, body temperature, hormone levels, blood pressure and heart activity, may also play a central role in drug addiction, according to a recent study published online by the Proceedings of the National Academy of Sciences (PNAS).

Drug helps for staying awake

For those battling the fatigue of working the graveyard shift, a new study suggests that a prescription drug approved for narcolepsy may reduce sleepiness and improve alertness for nocturnal employees.

Drug may help night-shift workers

Working at night and sleeping during the day is not natural for any human body, but some people have trouble adapting to such arrangements to the point where their distress qualifies as a medical disorder. Now, this underdiagnosed and difficult-to-treat condition is the subject of the first-ever clinical trial of the promising medication modafinil.

Teens Should Light Up - Their Glasses, That Is

Researchers say teens should wear orange tinted glasses on their way to school to reset their internal clocks.

Researchers catch up with the causes of jet lag

What that means, he says, is it is not just a matter of the whole body being out of time in the environment. It is as if the times of all the body's subclocks are out of sync as well.

New England Journal of Medicine Publishes First Clinical Study of Medication to Improve Wakefulness in Patients with Shift Work Sleep Disorder

"This is a very important first study demonstrating the value of an effective therapy for shift work sleep disorder and illustrates the need for further research to identify other effective therapies for these patients, whose sleepiness was not completely resolved with treatment," stated Charles A. Czeisler, PhD, MD, Professor of Sleep Medicine at Harvard Medical School and lead study author. "Patients with this under-recognized condition are just as sleepy at night as patients with narcolepsy or obstructive sleep apnea during the day."

Provigil of Modest Benefit for Shift-Work Sleep Disorder

3-Provigil (modafinil), a stimulant with an unknown mechanism, has been found to be of modest benefit in treating excessive sleepiness associated with shift-work sleep disorder, yet more effective therapies are needed, researchers here reported.

The Papalotzin Panopticon

Scientists only recently sorted out a major butterfly mystery: how Monarch butterflies have steered for millennia between eastern Canada's forests and central Mexico's mountains. It was known that the Monarchs use the angle of polarized sunlight to keep them on course, but researchers have discovered the mechanics of how this works. Special photoreceptors for ultraviolet light in butterfly eyes provide them with sense of direction. This sense connects with the circadian clock in the butterfly brain to both cue the creatures and direct them on their 3,400-odd mile migration.

Sleep Demons

Students can find their nightly rest interrupted by insomnia and sleeptalking

P.M. kids in an A.M. world

Why are teens so foggy early in the day?

Sleep Aid with Novel Mechanism Approved

A new insomnia treatment, approved by FDA July 22, is the first insomnia drug that was not designated a controlled substance by the Drug Enforcement Agency. Rozerem (ramelteon) is also the second sleep aid indicated for long-term use. Sepracor’s Lunesta (eszopiclone) was the first.

Protein controls metabolism and circadian rhythms

University of Toronto researchers have gained new insight into how a specific protein may control circadian rhythms and metabolic processes, which has implications for treating cholesterol-related diseases.

Sleep deprivation eats into child development

A sleep-deprived child may appear the opposite of sleepy -- so much so that he or she could end up being wrongly diagnosed with an attention deficit disorder

Melatonin Slows Cancer But Is Little Used

Despite growing evidence that melatonin significantly improves risk, survival, and performance status in patients with advanced cancer, it continues to be overlooked as a therapeutic option because it lacks US Food and Drug Administration (FDA) approval and requires administration at times of day inconvenient to physicians.

Teenager circadian rhythm

Many teens have trouble waking up in the morning for school, and their circadian clock may be to blame.

New insight into how protein E75 may control circadian rhythms and metabolic processes

University of Toronto researchers have gained new insight into how a specific protein may control circadian rhythms and metabolic processes, which has implications for treating cholesterol-related diseases.

Dad Knows Best Sometimes

All people follow a “body rhythm” that has them up at a particular time each morning, and bedding down at another particular time each night.

Age and sleep play catch-up

There's growing evidence that poor sleep can foster diseases that shorten life, says Fred Turek, director of the Center for Sleep and Circadian Biology at Northwestern University School of Medicine. Sleep problems can lead to biological changes that cause weight gain, increase diabetes risk, promote heart disease and worsen depression.

Putting Some Life Back into the Graveyard Shift

Imagine waking up every day at 9PM and heading to work until 3AM. Would you be able to adapt to working nights and sleeping when the sun is up? There's a reason they call it the graveyard shift, but for the 22 million shift workers in America, overnight jobs and constantly changing schedules are a reality that cannot be avoided.

Sleep, and other maladies

Sleep deprivation seems to be a favorite means of torture. Considered non-invasive, it still leaves scars on the psyche. Our circadian rhythms are disrupted, and this affects more than the body, as any medical student can affirm. Sleepless nights, whether in Seattle or not, can mean a terrible day. Polyphasic sleep, or short siestas can help ease the tiredness.

Drug treatment mimics circadian rhythms

UK company Diurnal has received orphan product designation from the European Commission for a novel treatment that uses a drug delivery technology to match the body’s circadian rhythms.

Battle against cancer hits home for project donor

How disruption to the body's circadian clock may be related to breast cancer development, and how the circadian clock may offer new ways to fight cancer.

Window treatments control light, privacy

Light is essential to life. Without light, there would be no life as we know it in our world. It's important not just for the plants in our home and garden, but also for our own emotional and physical health. Many people suffer from seasonal affective disorder when they are deprived of natural light during winter months.

Plant Circadian Clocks Increase Photosynthesis, Growth, Survival, and Competitive Advantage

Circadian clocks are believed to confer an advantage to plants, but the nature of that advantage has been unknown. We show that a substantial photosynthetic advantage is conferred by correct matching of the circadian clock period with that of the external light-dark cycle. In wild type and in long– and short–circadian period mutants of Arabidopsis thaliana, plants with a clock period matched to the environment contain more chlorophyll, fix more carbon, grow faster, and survive better than plants with circadian periods differing from their environment. This explains why plants gain advantage from circadian control.

Hormone melatonin may slow breast cancer: study

A new study is shedding more light on the possible link between breast cancer and lower levels of melatonin -- a hormone the body produces during darkness to help promote sleep.

Jennie Brand-Miller: GI Jennie

It may feel as though GI has all the hallmarks of this year's media hype. The health and lifestyle pages are forever reinventing themselves, and now everyone is sick to death of the Atkins and South Beach diets, they have hit upon GI as the Next Big Thing. But that's not quite the reality. The media may operate according to its own circadian rhythms and GI may fade from the public consciousness, but the hard science behind it dates back nearly 25 years and Brand-Miller has been in on it from the start.

Workbrain Unveils Real-Time Self-Scheduling for Healthcare

Workforce management innovator enables healthcare organizations to improve patient care while decreasing costs

Neurobiology of Mice Selected for High Voluntary Wheel-Running Activity

Selective breeding of house mice has been used to study the evolution of locomotor behavior. Our model consists of 4 replicate lines selectively bred for high voluntary wheel running (High- Runner) and 4 bred randomly (Control). The major changes in High- Runner lines appear to have taken place in the brain rather than in capacities for exercise. Their neurobiological profile resembles features of human Attention Deficit Hyperactivity Disorder (ADHD) and is also consistent with high motivation for exercise as a natural reward. Both ADHD and motivation for natural rewards (such as food and sex), as well as drugs of abuse, have been associated with alterations in function of the neuromodulator dopamine, and High-Runner mice respond differently to dopamine drugs. In particular, drugs that block the dopamine transporter protein (such as Ritalin and cocaine) reduce the high-intensity running of High- Runner mice but have little effect on Control mice.

Nuns carve pioneering life from the land

New Skete is more sensitive to people's circadian rhythms than many monasteries. There is no specific time for the sisters to read, pray or meditate, other than matins in the morning and vespers, at 5 p.m.

Woman Receives Chemotherapy While Rollerblading on Lakefront

McConnell received her chemotherapy via a new field of medicine, called chronotherapy. The term is from the Greek chronos, meaning time. Chronotherapy is medicine that takes the body"s natural rhythms into account.

Parasites' genetic code 'cracked'

Sleeping sickness disturbs a person's circadian rhythm so they stay awake at night and sleep during the day.

Around the clock

There's a good amount of research that has found human circadian rhythm favors a light/dark cycle, meaning that people are built to be up during the day and to sleep at night. At the very least, a nocturnal job challenges the way many people have been raised to live and work.

Scientists find clues to memory health

They wrote in the July 2005 issue of the Journal of the American Geriatric Society that senior adults have more difficulty getting a good night's sleep because the body's circadian rhythms change with age. Seniors also may experience insomnia as a side effect of one of the many medications prescribed to older adults.

Nuclear import of mPER3 in Xenopus oocytes and HeLa cells requires complex formation with mPER1

Several transcription factors with the function of setting the biological clock in vertebrates have been described. A detailed understanding of their nucleocytolasmic transport properties may uncover novel aspects of the regulation of the circadian rhythm. This assumption led us to perform a systematic analysis of the nuclear import characteristics of the different murine PER and CRY proteins, using Xenopus oocytes and HeLa cells as experimental systems. Our major finding is that nuclear import of mPER3 requires complex formation with mPER1. We further show that the nuclear localization signal (NLS) function of mPER1 and not activation of a masked NLS in mPER3 is critical for the import of the mPER1–mPER3 complex. Finally, and as previously described in other cell systems, nuclear import of mPER proteins in Xenopus oocytes correlates positively with their phosphorylation.

Serotonin may play a role in maintaining circadian rhythm

Researchers at the University of Pennsylvania School of Medicine have determined how serotonin decreases the body's sensitivity to light and that exposure to constant darkness leads to a decrease in serotonin levels in the brain of fruit flies.

Mood Lighting: Penn Researchers Determine Role Of Serotonin In Modulating Circadian Rhythm

Researchers at the University of Pennsylvania School of Medicine have determined how serotonin decreases the body's sensitivity to light and that exposure to constant darkness leads to a decrease in serotonin levels in the brain of fruit flies. These findings suggest that serotonin may play a role in maintaining circadian rhythm, as well as modulating light-related disorders such as seasonal affective disorder (SAD). Senior author Amita Sehgal, PhD, Professor of Neuroscience at Penn and a Howard Hughes Medical Institute (HHMI) Investigator, and colleagues report their findings in the July 7 issue of Neuron.

Category: ClockNews

Deep into Sleep

Here is an excellent article about sleep from Harvard Magazine.