Possible increase in cardiovascular disease and lung cancer mortality observed in nurses working rotating night shifts, according to report in the American Journal of Preventive Medicine
ELSEVIER HEALTH SCIENCES
Night shift work has been consistently associated with higher risk for cardiovascular disease (CVD) and cancer. In 2007 the World Health Organization classified night shift work as a probable carcinogen due to circadian disruption. In a study in the current issue of the American Journal of Preventive Medicine, researchers found that women working rotating night shifts for five or more years appeared to have a modest increase in all-cause and CVD mortality and those working 15 or more years of rotating night shift work appeared to have a modest increase in lung cancer mortality. These results add to prior evidence of a potentially detrimental effect of rotating night shift work on health and longevity.
Sleep and the circadian system play an important role in cardiovascular health and antitumor activity. There is substantial biological evidence that night shift work enhances the development of cancer and CVD, and contributes to higher mortality.
An international team of researchers investigated possible links between rotating night shift work and all-cause, CVD, and cancer mortality in a study of almost 75,000 registered U.S. nurses. Using data from the Nurses’ Health Study (NHS), the authors analyzed 22 years of follow-up and found that working rotating night shifts for more than five years was associated with an increase in all-cause and CVD mortality. Mortality from all causes appeared to be 11% higher for women with 6-14 or ?15 years of rotating night shift work. CVD mortality appeared to be 19% and 23% higher for those groups, respectively. There was no association between rotating shift work and any cancer mortality, except for lung cancer in those who worked shift work for 15 or more years (25% higher risk).
The NHS, which is based at Brigham and Women’s Hospital, began in 1976, with 121,700 U.S. female nurses aged 30-55 years, who have been followed up with biennial questionnaires. Night shift information was collected in 1988, at which time 85,197 nurses responded. After excluding women with pre-existing CVD or other than non-melanoma skin cancer, 74,862 women were included in this analysis. Defining rotating shift work as working at least three nights per month in addition to days or evenings in that month, respondents were asked how many years they had worked in this way. The prespecified categories were never, 1-2, 3-5, 6-9, 10-14, 15-19, 20-29, and ?30 years.
According to Eva S. Schernhammer, MD, DrPH, currently Associate Professor of Medicine, Harvard Medical School, and Associate Epidemiologist, Department of Medicine, Brigham and Women’s Hospital, Boston, this study “is one of the largest prospective cohort studies worldwide with a high proportion of rotating night shift workers and long follow-up time. A single occupation (nursing) provides more internal validity than a range of different occupational groups, where the association between shift work and disease outcomes could be confounded by occupational differences.”
Comparing this work with previous studies, she continues, “These results add to prior evidence of a potentially detrimental relation of rotating night shift work and health and longevity…To derive practical implications for shift workers and their health, the role of duration and intensity of rotating night shift work and the interplay of shift schedules with individual traits (e.g., chronotype) warrant further exploration.”
Source: American Journal of Preventive Medicine via EurekAlert
for their discoveries of cells that constitute a positioning system in the brain
How do we know where we are? How can we find the way from one place to another? And how can we store this information in such a way that we can immediately find the way the next time we trace the same path? This year´s Nobel Laureates have discovered a positioning system, an “inner GPS” in the brain that makes it possible to orient ourselves in space, demonstrating a cellular basis for higher cognitive function.
In 1971, John O´Keefe discovered the first component of this positioning system. He found that a type of nerve cell in an area of the brain called the hippocampus that was always activated when a rat was at a certain place in a room. Other nerve cells were activated when the rat was at other places. O´Keefe concluded that these “place cells” formed a map of the room.
More than three decades later, in 2005, May-Britt and Edvard Moser discovered another key component of the brain’s positioning system. They identified another type of nerve cell, which they called “grid cells”, that generate a coordinate system and allow for precise positioning and pathfinding. Their subsequent research showed how place and grid cells make it possible to determine position and to navigate.
The discoveries of John O´Keefe, May-Britt Moser and Edvard Moser have solved a problem that has occupied philosophers and scientists for centuries – how does the brain create a map of the space surrounding us and how can we navigate our way through a complex environment?
How do we experience our environment?
The sense of place and the ability to navigate are fundamental to our existence. The sense of place gives a perception of position in the environment. During navigation, it is interlinked with a sense of distance that is based on motion and knowledge of previous positions.
Questions about place and navigation have engaged philosophers and scientists for a long time. More than 200 years ago, the German philosopher Immanuel Kant argued that some mental abilities exist as a priori knowledge, independent of experience. He considered the concept of space as an inbuilt principle of the mind, one through which the world is and must be perceived. With the advent of behavioural psychology in the mid-20th century, these questions could be addressed experimentally. When Edward Tolman examined rats moving through labyrinths, he found that they could learn how to navigate, and proposed that a “cognitive map” formed in the brain allowed them to find their way. But questions still lingered – how would such a map be represented in the brain?
John O´Keefe and the place in space
John O´Keefe was fascinated by the problem of how the brain controls behaviour and decided, in the late 1960s, to attack this question with neurophysiological methods. When recording signals from individual nerve cells in a part of the brain called the hippocampus, in rats moving freely in a room, O’Keefe discovered that certain nerve cells were activated when the animal assumed a particular place in the environment (Figure 1). He could demonstrate that these “place cells” were not merely registering visual input, but were building up an inner map of the environment. O’Keefe concluded that the hippocampus generates numerous maps, represented by the collective activity of place cells that are activated in different environments. Therefore, the memory of an environment can be stored as a specific combination of place cell activities in the hippocampus.
May-Britt and Edvard Moser find the coordinates
May-Britt and Edvard Moser were mapping the connections to the hippocampus in rats moving in a room when they discovered an astonishing pattern of activity in a nearby part of the brain called the entorhinal cortex. Here, certain cells were activated when the rat passed multiple locations arranged in a hexagonal grid (Figure 2). Each of these cells was activated in a unique spatial pattern and collectively these “grid cells” constitute a coordinate system that allows for spatial navigation. Together with other cells of the entorhinal cortex that recognize the direction of the head and the border of the room, they form circuits with the place cells in the hippocampus. This circuitry constitutes a comprehensive positioning system, an inner GPS, in the brain (Figure 3).
A place for maps in the human brain
Recent investigations with brain imaging techniques, as well as studies of patients undergoing neurosurgery, have provided evidence that place and grid cells exist also in humans. In patients with Alzheimer´s disease, the hippocampus and entorhinal cortex are frequently affected at an early stage, and these individuals often lose their way and cannot recognize the environment. Knowledge about the brain´s positioning system may, therefore, help us understand the mechanism underpinning the devastating spatial memory loss that affects people with this disease.
The discovery of the brain’s positioning system represents a paradigm shift in our understanding of how ensembles of specialized cells work together to execute higher cognitive functions. It has opened new avenues for understanding other cognitive processes, such as memory, thinking and planning.
O’Keefe, J., and Dostrovsky, J. (1971). The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely‐moving rat. Brain Research 34, 171-175.
O´Keefe, J. (1976). Place units in the hippocampus of the freely moving rat. Experimental Neurology 51, 78-109.
Fyhn, M., Molden, S., Witter, M.P., Moser, E.I., Moser, M.B. (2004) Spatial representation in the entorhinal cortex. Science 305, 1258-1264.
Hafting, T., Fyhn, M., Molden, S., Moser, M.B., and Moser, E.I. (2005). Microstructure of spatial map in the entorhinal cortex. Nature 436, 801-806.
Sargolini, F., Fyhn, M., Hafting, T., McNaughton, B.L., Witter, M.P., Moser, M.B., and Moser, E.I. (2006). Conjunctive representation of position, direction, and velocity in the entorhinal cortex. Science 312, 758-762.
John O’Keefe was born in 1939 in New York City, USA, and holds both American and British citizenships. He received his doctoral degree in physiological psychology from McGill University, Canada in 1967. After that, he moved to England for postdoctoral training at University College London. He has remained at University College and was appointed Professor of Cognitive Neuroscience in 1987. John O´Keefe is currently Director of the Sainsbury Wellcome Centre in Neural Circuits and Behaviour at University College London.
May-Britt Moser was born in Fosnavåg, Norway in 1963 and is a Norwegian citizen. She studied psychology at the University of Oslo together with her future husband and co-Laureate Edvard Moser. She received her Ph.D. in neurophysiology in 1995. She was a postdoctoral fellow at the University of Edinburgh and subsequently a visiting scientist at University College London before moving to the Norwegian University of Science and Technology in Trondheim in 1996. May-Britt Moser was appointed Professor of Neuroscience in 2000 and is currently Director of the Centre for Neural Computation in Trondheim.
Edvard I. Moser was born in born 1962 in Ålesund, Norway and has Norwegian citizenship. He obtained his Ph.D. in neurophysiology from the University of Oslo in 1995. He was a postdoctoral fellow together with his wife and co‐Laureate May‐Britt Moser, first at the University of Edinburgh and later a visiting scientist in John O´Keefe´s laboratory in London. In 1996 they moved to the Norwegian University of Science and Technology in Trondheim, where Edvard Moser became Professor in 1998. He is currently Director of the Kavli Institute for Systems Neuroscience in Trondheim.
Lowering internal eye pressure is currently the only way to treat glaucoma. A tiny eye implant developed by Stephen Quake’s lab could pair with a smartphone to improve the way doctors measure and lower a patient’s eye pressure.
BY BJORN CAREY
For the 2.2 million Americans battling glaucoma, the main course of action for staving off blindness involves weekly visits to eye specialists who monitor – and control – increasing pressure within the eye.
Now, a tiny eye implant developed at Stanford could enable patients to take more frequent readings from the comfort of home. Daily or hourly measurements of eye pressure could help doctors tailor more effective treatment plans.
Internal optic pressure (IOP) is the main risk factor associated with glaucoma, which is characterized by a continuous loss of specific retina cells and degradation of the optic nerve fiber. The mechanism linking IOP and the damage is not clear, but in most patients IOP levels correlate with the rate of damage.
Reducing IOP to normal or below-normal levels is currently the only treatment available for glaucoma. This requires repeated measurements of the patient’s IOP until the levels stabilize. The trick with this, though, is that the readings do not always tell the truth.
Like blood pressure, IOP can vary day-to-day and hour-to-hour; it can be affected by other medications, body posture or even a neck-tie that is knotted too tightly. If patients are tested on a low IOP day, the test can give a false impression of the severity of the disease and affect their treatment in a way that can ultimately lead to worse vision.
The new implant was developed as part of a collaboration between Stephen Quake, a professor of bioengineering and of applied physics at Stanford, and ophthalmologist Yossi Mandel of Bar-Ilan University in Israel. It consists of a small tube – one end is open to the fluids that fill the eye; the other end is capped with a small bulb filled with gas. As the IOP increases, intraocular fluid is pushed into the tube; the gas pushes back against this flow.
As IOP fluctuates, the meniscus – the barrier between the fluid and the gas – moves back and forth in the tube. Patients could use a custom smartphone app or a wearable technology, such as Google Glass, to snap a photo of the instrument at any time, providing a critical wealth of data that could steer treatment. For instance, in one previous study, researchers found that 24-hour IOP monitoring resulted in a change in treatment in up to 80 percent of patients.
The implant is currently designed to fit inside a standard intraocular lens prosthetic, which many glaucoma patients often get when they have cataract surgery, but the scientists are investigating ways to implant it on its own.
“For me, the charm of this is the simplicity of the device,” Quake said. “Glaucoma is a substantial issue in human health. It’s critical to catch things before they go off the rails, because once you go off, you can go blind. If patients could monitor themselves frequently, you might see an improvement in treatments.”
Remarkably, the implant won’t distort vision. When subjected to the vision test used by the U.S. Air Force, the device caused nearly no optical distortion, the researchers said.
Before they can test the device in humans, however, the scientists say they need to re-engineer the device with materials that will increase the life of the device inside the human eye. Because of the implant’s simple design, they expect this will be relatively achievable.
“I believe that only a few years are needed before clinical trials can be conducted,” said Mandel, head of the Ophthalmic Science and Engineering Laboratory at Bar-Ilan University, who collaborated on developing the implant.
The work, published in the current issue of Nature Medicine, was co-authored by Ismail E. Araci, a postdoctoral scholar in Quake’s lab, and Baolong Su, a technician in Quake’s lab and currently an undergraduate student at the University of California, Los Angeles.