Stress at Night May Be More Stressful

MedicalResearch.com Interview with:

Yujiro Yamanaka, Ph.D. Associate Professor Hokkaido University Graduate School of Education Sapporo, Japan 

Dr. Yamanaka

Yujiro Yamanaka, Ph.D.
Associate Professor Hokkaido University
Graduate School of Education
Sapporo, Japan 

MedicalResearch.com: What is the background for this study?

Response: My laboratory has focused on the human circadian rhythms in particularly investigating the time of day effect of non-photic cues especially physical exercise and psychological stressor on circadian rhythms.

In mammals including humans, the central circadian pacemaker is located in the suprachiasmatic nucleus (SCN) in the brain hypothalamus. The SCN entrains to an external light-dark cycle and generates endogenous 24 h rhythmicity in body function. The hypothalamic-pituitary-adrenal (HPA) axis is our major stress response system. We can assess the response of HPA axis to psychological stress event by measuring the level of glucocorticoid hormone, cortisol in saliva. The cortisol shows clear circadian rhythm with higher levels in the morning and lower levels in the evening. This rhythm is generated by the SCN circadian pacemaker.

Previous study (Kudielka et al. Psychoneuroendocrinology 2004) could demonstrate that the cortisol stress level is significantly elevated by acute psychological stress event in the morning (9 a.m. to 10 a.m.) and afternoon (3 p.m. to 4 p.m.). However, there are no study examining the effect of evening psychological stress event on the HPA axis activity. Thus, our new study focused on examining whether the HPA axis differentially responses to morning and evening stress event in healthy subjects.

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Spring Daylight Savings Time Linked to More AFib Admissions

MedicalResearch.com Interview with:
sunset copyright American Heart AssociationJay Chudow, M.D.

Montefiore Medical Center
Bronx, New York

MedicalResearch.com: What is the background for this study? What are the main findings?

  • Others found associations between daylight saving time transitions and sleep duration, sleep quality, workplace injuries and traffic accidents. Regarding cardiovascular health, studies in Europe and the United States have found an increased incidence of acute myocardial infarction and ischemic stroke in the days following daylight saving time transitions.
  • Our study found a significant increase in admissions for atrial fibrillation following the daylight saving time spring transition compared to the yearly average (average of 3.13 vs 2.56 admissions per day over the Monday to Thursday period). No significant difference was found following the autumn transition.
  • These findings add atrial fibrillation as a known condition associated with daylight saving time transitions. It adds to the knowledge base of negative health consequences of daylight saving time. 

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Early Dinner May Lower Cancer Risk

MedicalResearch.com Interview with:
“Christmas Roast and Ham Dinner. Had Tamales for Christmas Eve and Christmas morning. #Roast #Ham #ChristmasDinner #Christmas #Champagne #Dinner #Foodstagram” by Yvonne Esperanza is licensed under CC BY 2.0Manolis Kogevinas, MD, PhD

Research Professor
NCDs & Environment Group
Barcelona Institute for Global Health (ISGlobal) – Campus MAR
Barcelona Biomedical Research Park (PRBB) (office 194)
Barcelona, Spain

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We did the study for two main reasons.

(i) breast and to a less extent prostate cancer are the cancers that have been associated with night shift work and resulting circadian disruption (disruption of the natural day-light cycle);

(ii) experimental studies in animals indicate that timing of diet is important. For example, giving an hypercaloric diet to mice during the day results in obesity, while giving the same diet during the night does not. Mice are nocturnal animals and this means that there normal eating time is the night when they can metabolise what they eat. So, would something similar affect humans? When we eat in late hours at a time when “normally” (normally in the sense of evolution) we would be resting.

In this study we show that adherence to a more diurnal eating pattern and specifically an early supper and a long interval between last meal and sleep are associated with a lower breast and prostate cancer risk. Specifically having super before 9pm and having an interval of 2 hours between the last big meal and sleep, were both associated with an approximately 20% prevention of breast and prostate cancer) compared to those who have supper after 10pm or those who eat and then sleep very close after supper.

Also, the strongest protection was found in “morning types” as compared to “evening types”. Morning types are expected to function worse than evening types in late evening so late suppers may have more adverse effects on them.

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Digestive Organs Have Separate Biologic Clocks From Brain’s Master Clock

MedicalResearch.com Interview with:

Dr. Hans Van Dongen, PhD Director of the Sleep and Performance Research Center. ELSON S. FLOYD COLLEGE OF MEDICIN Washington State University Spokane, WA

Dr. VAN DONGEN

Dr. Hans Van Dongen, PhD
Director of the Sleep and Performance Research Center.
ELSON S. FLOYD COLLEGE OF MEDICIN
Washington State University
Spokane, WA

MedicalResearch.com: What is the background for this study?

Response: Night shift workers are at increased risk of metabolic disorders, including obesity and type 2 diabetes, as well as cardiovascular disease, chronic kidney disease, and cancer. Although it is believed that the biological clock – the master circadian clock in the brain – plays an important role in these adverse chronic health consequences of night shift work, the underlying mechanisms are not well understood. Continue reading

Disturbed Circadian Rhythm Associated With Poor Mental Health

MedicalResearch.com Interview with:

Laura Lyall  MA; MSc; PhD Research Associate Institute of Health and Wellbeing University of Glasgow

Dr. Lyall

Laura Lyall  MA; MSc; PhD
Research Associate
Institute of Health and Wellbeing
University of Glasgow 

MedicalResearch.com: What is the background for this study?  

Response: Previous studies have suggested a link between disturbed circadian rhythms and depression and bipolar disorder. These studies have however usually used small samples, subjective measures of circadian disruption, or have not accounted for potential confounding factors like sociodemographic and lifestyle characteristics. The UK Biobank cohort has accelerometry (activity monitor) data as well as mental health, lifestyle, BMI and sociodemographic data for over 91,000 individuals, and means we can address this question using objective measures of circadian rhythmicity on a large scale.

We derived a measure of relative amplitude from the UK Biobank’s accelerometry data, which was recorded for 7 days between 2013-2014 from around 100,000 participants. Relative amplitude reflects the distinction, in terms of activity levels, between an individual’s most active 10 hours and least active 5 hours, in an average day. If an individual is inactive during the day, or has disturbed sleep at night, the will show low relative amplitude, consistent with disturbed circadian rest-activity patterns.

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As We Age, Our Circadian Clock Becomes Less Sensitive To Light, Leading To Sleep Problems

MedicalResearch.com Interview with:
“Woman sleeping” by Timothy Krause is licensed under CC BY 2.0Dr Gurprit S. Lall BSc, MSc, PhD, PGCHE, FHEA

Medway School of Pharmacy
Interim Deputy Head of School
Senior Lecturer in Pharmacology
Director of Graduate Studies (Research),
University of Kent at Medway
Chatham Maritime, Chatham, Kent

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Medical advancement in prevention and diagnosis of disease has increased life expectancy significantly, thus generating an ageing population far greater than previously seen.  Because of this, it is essential that we begin to understand the ageing process, together with the health implications associated with senescence.  Recent research has found that changes in the circadian clock, located in the brain, play a contributing role in the decline of many physiological and behavioural traits observed through the ageing process.  One example of this, which is commonly seen in the elderly is a decline in sleep-wake cycle regulation; typically presenting as disrupted sleeping patterns.

The circadian clock, in mammals, possesses the ability to integrate our social lifestyle choices with the environmental day-night cycle to generate a 24-hour rhythm to which our physiological functions are synchronised.  It is this synchronisation that plays a vital role in regulating many of our behavioural outputs, such as sleeping-wake patterns.  This clock takes its strongest timing cue from the natural day night cycle governed by the duration of daily sunlight.

Our study investigated the changes in the interpretation of this light signal by the circadian clock as we age and its impact on function.  We found that the clock became less responsive to light stimuli at both the level of clock cells and at driving behavioural activity.  We were able to narrow this down to changes in the proteins within cells that relay light information to the molecular time setting machinery.  In detail, light signals are relayed to the clock through an excitatory neurotransmitter called glutamate and this signal is predominantly relayed through NMDA receptors located on the surface of clock cells.  It is the configuration of the NMDA receptor that alters as we age and this leads to the clock becoming less responsive to light.

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Fragmented Circadian Rhythm Associated with Preclinical Alzheimer’s Disease

MedicalResearch.com Interview with:
“mirror clock” by tourist_on_earth is licensed under CC BY 2.0Yo-El Ju, MD

Assistant Professor of Neurology
Sleep Medicine Section
Washington University School of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The background for this study is that prior studies have shown that people with Alzheimer’s Disease have poor circadian clock function, for example sleeping during the day and being awake or agitated at night. Autopsy studies have shown that people with Alzheimer’s Disease have degeneration in the “clock” part of their brains. In this study, we wanted to examine whether there were any circadian problems much earlier in Alzheimer’s Disease, when people do not have any memory or thinking problems at all.

We measured circadian function in 189 people with an actigraph, which is an activity monitor worn like a watch, for 1-2 weeks. Brain scans and studies of cerebrospinal fluid were used to determine who had preclinical Alzheimer’s Disease, meaning they have the brain changes of Alzheimer’s but do not have symptoms yet.  Continue reading

Matching Time of Day To Patient’s Biorhythm May Improve Surgical Outcomes

MedicalResearch.com Interview with:
Prof David Montaigne MD

Faculté de Médecine de Lille H Warembourg
Lille, France

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It is well known for many decades that cardiovascular diseases exhibit a diurnal variation with for instance higher incidence of myocardial infarction in the early morning as opposed to the evening. Although studies on circadian gene knock-out and mutant mice argue for a biorhythm in myocardial ischemia-reperfusion tolerance, whether a biorhythm in the myocardial tolerance to ischemia, exists in humans was unclear because of conflicting reports in the context of myocardial infarction.

We demonstrated for the first time in humans that the myocardial tolerance to ischemia-reperfusion is different along the day, in line with rodent experiments performed in the early 2010s.

We demonstrated that this biorhythm is clinically meaningful and that it can be targeted as a cardioprotective strategy.

In this topic, Rever-alpha is of specific interest. It belongs at the same time to circadian genes and nuclear receptor families: being a nuclear receptor, it is a feasible pharmacological target, conversely to other circadian genes.

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Considering Circadian Rhythms May Aide in Diagnosis of Consciousness Disorders

MedicalResearch.com Interview with:

Copyright Anna-Lisa Bexten Dr. Christine Blume PhD Post-Doctoral Researcher University of Salzburg Centre for Cognitive Neuroscience (CCNS) Laboratory for Sleep, Cognition & Consciousness Research Salzburg

Dr. Christine Blume

Dr. Christine Blume PhD
Post-Doctoral Researcher
University of Salzburg
Centre for Cognitive Neuroscience (CCNS)
Laboratory for Sleep, Cognition & Consciousness Research
Salzburg

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We are governed by rhythmic processes. Many of these processes follow a circadian pattern, that is, they have a period length of approximately 24 hours and are under tight control of a biological master clock located in the suprachiasmatic nucleus of the hypothalamus. Given the circadian variation in global states like alertness, it is not surprising that consciousness also varies rhythmically in healthy individuals, it follows the sleep-wake cycle.

From a clinical perspective, misalignment of circadian rhythms, which occurs when the sleep-wake schedule is at odds with the light-dark cycle as in the case of night shifts, can cause considerable stress, have detrimental effects on the immune system and impair cognitive abilities. Despite the knowledge that entrained circadian rhythms are important for healthy body and brain functioning, very little is known about circadian rhythms in patients diagnosed with a disorder of consciousness (DOC) following severe brain injuries. We argue that studying circadian rhythms in DOC patients may be especially interesting and important for two reasons.

First, the presence or absence of circadian rhythms as well as anomalies in them could be informative about the state of the patient as well as their potential for recovery.

Second, this could provide information about time points that best capture remaining cognitive functions thereby minimising the risk of misdiagnoses.

Beyond this, examining circadian processes may also provide targets for therapeutic interventions such as light stimulation, which has proven successful in individuals with e.g. circadian sleep disorders. Interestingly, analyses with Lomb-Scargle periodograms revealed significant circadian rhythmicity in all patients (range 23.5-26.3h).

We found that especially scores on the arousal subscale of the Coma Recovery Scale-Revised (CRS-R) were closely linked to the integrity of circadian variations in body temperature.

Finally, we piloted whether bright light stimulation could boost circadian rhythmicity and found positive evidence in two out of eight patients.

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Late Risers Eat More Fat and Sugar In Evening

MedicalResearch.com Interview with:
Mirkka Maukonen

MSc (nutrition), PhD Candidate
the National Institute for Health and Welfare, Department of Public Health Solutions
Helsinki, Finland

MedicalResearch.com: What is the background for this study?

Response: Recent literature has highlighted the importance of sleep and circadian rhythms in development of obesity and metabolic dysfunctions. Furthermore, it has been suggested that in addition to quality of the diet also meal timing may play role in development of obesity. For example, skipping breakfast and eating at later times in the evening have been associated with higher BMI. However, little is known about how the timing of circadian rhythms (chronotype) affects timing of energy intake and its association with metabolic health.

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By Interacting with Melatonin, Insecticides Could Disrupt Circadian Rhythm

MedicalResearch.com Interview with:

Rajendram Rajnarayanan PhD Department of Pharmacology and Toxicology Assistant Professor Jacobs School of Medicine and Biomedical Sciences University of Buffalo

Dr. Rajendram Rajnarayanan

Rajendram Rajnarayanan PhD
Department of Pharmacology and Toxicology
Assistant Professor
Jacobs School of Medicine and Biomedical Sciences
University of Buffalo

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Human exposure to environmental chemicals i.e., insecticides and pesticides increases the risk of various diseases by directly interacting with proteins or signaling pathways in the endocrine or neuroendocrine system. In this study, our teamscience effort integrating big-data computation with receptor pharmacology, report for the first time that carbamate insecticides found in household and agricultural products interact with human melatonin receptors.

At UB we have generated a database, we call it Chem2Risk, which contains about four million chemicals reported to have some level of toxicity. From those, after grouping the chemicals in clusters according to their similarity, we found several with potential to mimic melatonin. Wet-lab experiments confirmed that these chemicals indeed interact with melatonin receptors and have the potential to alter melatonin signaling. Continue reading

Morning People May Make More Mistakes After A Long Day

MedicalResearch.com Interview with:

Dr. Nicola Barclay, BA(Hons), MSc, PhD. Lecturer in Sleep Medicine Sleep and Circadian Neuroscience Institute (SCNi) Nuffield Department of Clinical Neurosciences Sir William Dunn School of Pathology University of Oxford

Dr. Nicola Barclay

Dr. Nicola Barclay, BA(Hons), MSc, PhD.
Lecturer in Sleep Medicine
Sleep and Circadian Neuroscience Institute (SCNi)
Nuffield Department of Clinical Neurosciences
Sir William Dunn School of Pathology
University of Oxford

MedicalResearch.com: What is the background for this study?

Response: We know that extreme sleep deprivation impairs our cognitive functions, particularly attention. This impairment in attention is likely to be driven by physiological mechanisms that change across the waking day (increasing sleep pressure), but also by factors associated with our biological clock. The timing of physiological processes particularly related to attention differ between morning and evening type people (our so called early morning larks and night owls), and so we hypothesised that morning and evening types would differ in their impairments in attention at different times of day, prior to and following 18 hours of sustained wakefulness.

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Late Sleepers Don’t Have Higher BMI

MedicalResearch.com Interview with:

Kelly Glazer Baron, PhD, MPH, C. B.S.M. Diplomate, Academy of Cognitive Therapy Northwestern University Feinberg School of Medicine Chicago, IL 60611

Dr. Kelly Glazer Baron

Kelly Glazer Baron, PhD, MPH, C. B.S.M.
Diplomate, Academy of Cognitive Therapy
Northwestern University
Feinberg School of Medicine
Chicago, IL 60611

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In contrast to several previous studies, being a late sleeper was not associated with higher BMI (good news for late sleepers!!) but it was associated with less healthy behaviors, more fast food, fewer vegetables, lower dairy. It may be possible that these late sleepers who are able to get enough sleep can compensate for their poor diet by controlling overall calories or it could possibly lead to weight gain over time if their habits continue over time.

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Shift Work May Increase Risk of Stroke

MedicalResearch.com Interview with:

David Earnest, Ph.D. Professor in the Department of Neuroscience and Experimental Therapeutics Texas A&M Health Science Center College of Medicine

Dr. David Earnest

David Earnest, Ph.D.
Professor in the Department of Neuroscience and Experimental Therapeutics
Texas A&M Health Science Center College of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Earnest: When body clocks are disrupted, as they are when people engage in shift work or go to bed and get up at radically different times every few days, more severe ischemic strokes can result.

MedicalResearch.com: What should readers take away from your report?

Dr. Earnest:  Whenever possible, go to bed and get up at the same time each day and keep regular mealtimes. If you do need to keep an irregular schedule, it is especially important to be mindful of stroke risk and try especially hard to eliminate other risk factors, such as hypertension and obesity.

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Sleep Disturbance in Glaucoma Patients Due To Retinal Ganglion Cell Death

MedicalResearch.com Interview with: Carolina P B Gracitelli, M.D. Ophthalmology - PhD Candidate/ Research Fellow University of California San Diego - Hamilton Glaucoma Center  Medical Research: What is the background for this study? What are the main findings?  Dr. Gracitelli:  Of all the diseases that can lead to blindness, glaucoma is one of the most important diseases; it affects more than 70 million people worldwide, of whom approximately 10 % are bilaterally blind. Different studies have reported that the damage caused by glaucomatous disease lead to retinal ganglion cell (RGC) loss and consequently loss of intrinsically photosensitive retinal ganglion cells (ipRGCs), which is a subtype of RGC. This subpopulation of RGC is clearly related with non-image-forming visual function such as photic synchronization of circadian rhythms  and the pupillary light reflex. However, the true impact of glaucoma on sleep quality, sleep disturbance or circadian rhythm was until nowadays controversial. The main clinical finding of our study was that glaucoma leads to RGC death, including ipRGC death. These cells are connected to several non-image-forming functions, including circadian photoentrainment and pupillary reflexes. Therefore, the image-forming and non-image-forming visual systems are associated with glaucoma. Circadian function has not been well investigated in clinical daily practice, but it can interfere with the quality of life of these patients. Concerns about sleep disturbances in glaucoma patients should be incorporated into clinical evaluations.   Medical Research: What should clinicians and patients take away from your report? Dr. Gracitelli:  Our data support the concept that glaucoma is associated with a loss of ipRGCs that mediate the pupillary light response, particularly to the sustained component of the blue flash with a luminance of 250 cd/m2. Additionally, glaucoma patients had significant sleep disturbances that were inversely correlated with a measure of ipRGC function, the pupillary light reflex. These results suggest that the loss of ipRGCs in glaucoma may also lead to sleep disturbances. Both non-visual functions of ipRGCs are correlated, indicating that attention should be paid to the non-image forming visual functions in glaucoma patients.   Medical Research: What recommendations do you have for future research as a result of this study?  Dr. Gracitelli:  Sleep disorders is a complex system, therefore, some conclusions in this study should be carefully evaluated. Further studies with larger cohorts could also help to elucidate the association between the pupillary reflex and the polysomnography parameters. And longitudinal studies can better explain the associations between sleep disorders and glaucoma progression.  In addition, we know that there are several types of ipRGCs and they have specific functions (pupillary reflex or circadian rhythms), therefore, evaluations would also need to include a more thorough assessment to understand better the specific role of ipRGCs in sleep disturbances. However, it is true that these ipRGCs functions are impaired in glaucoma, affecting the quality of life of these patients.   Citation:   Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep Quality in Patients with Glaucoma  Gracitelli, Carolina P.B. et al. Ophthalmology Published Online: April 06, 2015 DOI: http://dx.doi.org/10.1016/j.ophtha.2015.02.030MedicalResearch.com Interview with:
Carolina P B Gracitelli, M.D.
Ophthalmology – PhD Candidate/ Research Fellow
University of California San Diego – Hamilton Glaucoma Center

Medical Research: What is the background for this study? What are the main findings?

Dr. Gracitelli: Of all the diseases that can lead to blindness, glaucoma is one of the most important diseases; it affects more than 70 million people worldwide, of whom approximately 10 % are bilaterally blind. Different studies have reported that the damage caused by glaucomatous disease lead to retinal ganglion cell (RGC) loss and consequently loss of intrinsically photosensitive retinal ganglion cells (ipRGCs), which is a subtype of retinal ganglion cell. This subpopulation of RGC is clearly related with non-image-forming visual function such as photic synchronization of circadian rhythms and the pupillary light reflex. However, the true impact of glaucoma on sleep quality, sleep disturbance or circadian rhythm was until nowadays controversial.

The main clinical finding of our study was that glaucoma leads to retinal ganglion cell death, including ipRGC death. These cells are connected to several non-image-forming functions, including circadian photoentrainment and pupillary reflexes. Therefore, the image-forming and non-image-forming visual systems are associated with glaucoma. Circadian function has not been well investigated in clinical daily practice, but it can interfere with the quality of life of these patients. Concerns about sleep disturbances in glaucoma patients should be incorporated into clinical evaluations.

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Leg Cramps Peak in Summer, Dip in Winter

Scott R. Garrison MD PhD Associate Professor, Department of Family Medicine Director, Pragmatic Trials Collaborative Faculty of Medicine University of Alberta EdmontonMedicalResearch.com Interview with:
Scott R. Garrison MD PhD

Associate Professor, Department of Family Medicine
Director, Pragmatic Trials Collaborative
Faculty of Medicine University of Alberta Edmonton

MedicalResearch: What is the background for this study? What are the main findings?

Dr. Garrison: Nocturnal leg cramps (also called rest cramps) are painful muscle tightenings, most often in the legs or feet, that are brought on by rest and often wake the sufferer from sleep. They are very common in older adults and can also occur during pregnancy. Having read anecdotal mention that the rest cramps of pregnancy appeared to be worse in summer we sought cohort level evidence to determine whether the more common presentation of age-related rest cramps was also seasonal. To do this we primarily looked at new quinine starts in the province of British Columbia over a period of several years. British Columbia has a publicly funded health care system and maintains electronic records on all health services, including prescription drugs, provided to its roughly 4.2 million residents. Quinine is approved for the treatment of acute malaria in Canada but is instead almost exclusively used off-label to prevent rest cramps. As such, new quinine starts are an excellent marker for new or escalating cramp burden. We also looked at Internet searches, geographically limited to the USA, for the term “leg cramps” (reflecting public interest) obtained from the Google Trends Search Volume Index Tool. Seasonality for both of these indicators of cramp burden was assessed by determining how well a least squares minimizing sinusoidal model predicted variability.

We found that quinine starts and “leg cramp” related Internet queries were both strikingly sinusoidal with a 365-day periodicity (mid-summer high, mid-winter low) and a peak-to-peak variability that is approximately 2/3 of the mean. Seasonality accounted for 88% of the observed monthly variability (p < 0.0001) in quinine starts, and 70% of the observed variability (p < 0.0001) in “leg cramp” related internet searches. Continue reading

Key Clock Genes Linked To Alcohol Use and Abuse

Timo Partonen MD, Research Professor National Institute for Health and Welfare Helsinki, FinlandMedicalResearch.com Interview with:
Timo Partonen MD, Research Professor

National Institute for Health and Welfare
Helsinki, Finland

Medical Research: What is the background for this study? What are the main findings?

Response: Alcohol-use disorders are often comorbid conditions with mood and anxiety disorders. Clinical studies have demonstrated that there are abnormalities in circadian rhythms and intrinsic clocks in patients with alcohol-use disorders. Circadian clock gene variants are therefore a fruitful target of interest.

The main findings are that variants of key clock genes, namely those of ARNTL, ARNTL2, PER1 and PER2, have association with alcohol consumption, with alcohol abuse, or with alcohol dependence. It is of interest that variants of a fifth clock gene of key importance, that is those of CLOCK, are associated with alcohol-use disorders only if comorbid with depressive disorders.

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Shift Work May Reduce Cognitive Performance

Dr. Philip Tucker Department of Psychology | Yr Adran Seicoleg College of Human and Health Sciences | Coleg y Gwyddorau Dynol ac lechyd Swansea University | Prifysgol Abertawe Singleton Park | Parc Singleton Swansea | Abertawe  Medical Research: What is the background for this stuMedicalResearch.com Interview with:
Dr. Philip Tucker
Department of Psychology | Yr Adran Seicoleg
College of Human and Health Sciences | Coleg y Gwyddorau Dynol ac lechyd
Swansea University | Prifysgol Abertawe
Singleton Park | Parc Singleton Swansea | Abertawe

Medical Research: What is the background for this study? What are the main findings?

Dr. Tucker: Shift work, like jet-lag, is known to disrupt workers’ normal circadian rhythms (i.e. their body clocks) and their social life. It is also associated with greater risk of developing ulcers, cardiovascular disease, metabolic syndrome, breast cancer and reproductive problems. Several studies have also shown that shift workers experience heightened fatigue and sleepiness, particularly at night, and this may affect job performance and safety. However, very little is known about the long-term consequences of shift work on cognitive abilities. We followed a large sample of shift workers and non-shift workers over 10 years, testing their cognitive performance every 5 years. We found that the shift workers’ cognitive performance was lower than that of the day workers.  The difference was greatest for those who had worked shifts for more than 10 years. The shift workers’ cognitive function recovered after they quit shift work, but this recovery took at least 5 years from time that they stopped working shifts. The effects could not be attributed to poorer sleep quality among shift workers. Rather, it seems likely that the findings reflect the disruption of the shift workers’ circadian rhythms, which as been shown by other researchers to have an impact on brain structures involved in cognition and mental health over the lifespan.

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Shift Work May Raise Risk of Diabetes

Professor  Zuxun Lu School of Public Health Tongii Medical College Huazhong University of Science and Technology Wuhun, Hubei, China.MedicalResearch.com Interview with:
Professor  Zuxun Lu
School of Public Health
Tongii Medical College
Huazhong University of Science and Technology
Wuhun, Hubei, China.

Medical Research: What are the main findings of the study?

Prof. Lu: The main finding of this systematic review and meta-analysis was that shift work is associated with an increased risk of diabetes mellitus (DM). The association between shift work and DM appeared to be independent of physical activity, family of history of DM and body mass index. We found that the increased risk of diabetes mellitus was more pronounced in rotating shift group and male shift workers than in other shift group and female shift workers, respectively.
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Night Light May Drive Breast Cancer Growth

MSteven M. Hill, Ph.D. Professor, Structural & Cellular Biology Edmond & Lily Safra Chair for Breast Cancer Research Co-Director, Molecular Signaling Program, Louisiana Cancer Research Consortium Director, Tulane Circadian Biology CenteredicalResearch.com Interview with
Steven M. Hill, Ph.D.
Professor, Structural & Cellular Biology
Edmond & Lily Safra Chair for Breast Cancer Research
Co-Director, Molecular Signaling Program, Louisiana Cancer Research Consortium
Director, Tulane Circadian Biology Center

Medical Research: What are the main findings of the study?

Dr. Hill: The main findings of our study are that exposure to even dim light at night can drive human breast tumors to a hyper metabolic state, activating key tumor cell signaling pathways involved in tumor cell survival and proliferation, leading to increased tumor growth, all resulting in a tumor which is completely resistant to tamoxifen therapy. Our work shows that this effect is due to the repression of nighttime melatonin by dim light at night. When nighttime melatonin is replace the tumors become sensitive to tamoxifen resulting in cell death and tumor regression.
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High Fat & Sugar Diet May Disrupt Bowel Circadian Rhythm and Bacteria

Dr. Robin Voigt PhD Department of Internal Medicine Division of Gastroenterology Rush University Medical Center Chicago, IllinoisMedicalResearch.com Interview with:
Dr. Robin Voigt PhD
Department of Internal Medicine
Division of Gastroenterology
Rush University Medical Center
Chicago, Illinois

MedicalResearch: What are the main findings of the study? 

Dr. Voigt: We found that chronic circadian rhythm disruption has no effect on the intestinal microbiota when mice are fed a standard chow diet but when combined with a high-fat, high-sugar diet circadian rhythm disruption results in intestinal dysbiosis and an increase in pro-inflammatory bacteria.
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Scientists create small molecules that alter biological clock and lead to weight loss

The new molecules could lead to unique treatments for obesity, diabetes, high cholesterol, and sleep disorders

JUPITER, FL — Scientists from the Florida campus of The Scripps Research Institute have synthesized a pair of small molecules that dramatically alter the core biological clock in animal models, highlighting the compounds’ potential effectiveness in treating a remarkable range of disorders—including obesity, diabetes, high cholesterol, and serious sleep disorders.

The study was published on March 29, 2012, in an advance, online edition of the journal Nature.

The study showed that when administered in animal models the synthetic small molecules altered circadian rhythm and the pattern of core clock gene expression in the brain’s hypothalamus, the site of the master cellular clock that synchronizes daily rhythms in mammals; circadian rhythms are the physiological processes that respond to a 24-hour cycle of light and dark and are present in most living things.

When given to diet-induced obese mice, these same small molecules decreased obesity by reducing fat mass and markedly improving cholesterol levels and hyperglycemia—chronically high blood sugar levels that frequently lead to diabetes.

“The idea behind this research is that our circadian rhythms are coupled with metabolic processes and that you can modulate them pharmacologically,” said Thomas Burris, a professor at Scripps Florida who led the study. “As it turns out, the effect of that modulation is surprisingly positive—everything has been beneficial so far.”

Burris stressed that these compounds were first generation—the first to hit their targets in vivo with room for improvement as potential treatments. “In terms of therapeutics, this is really the first step,” he said.

In the new study, the team identified and tested a pair of potent synthetic compounds that activate proteins called REV-ERBα and REV-ERBβ, which play an integral role in regulating the expression of core clock proteins that drive biological rhythms in activity and metabolism.

In the study, the scientists observed clear metabolic effects when the synthetic compounds were administered twice a day for 12 days. Animals displayed weight loss due to decreased fat mass with no changes in the amount of food they ate. The animals followed the human model of obesity closely, eating a standard Western diet of high fat, high sugar foods, yet still lost weight when given the compounds.

In one of the study’s more striking findings, both synthetic compounds were shown to reduce cholesterol production. Cholesterol in the blood of treated animal models decreased 47 percent; triglycerides in the blood decreased 12 percent.

The circadian pattern of expression of a number of metabolic genes in the liver, skeletal muscle, and in fat tissue was also altered, resulting in increased energy expenditure, something of a surprise. In the study, the scientists observed a five percent increase in oxygen consumption, suggesting increased energy expenditure during the day and at night. However, these increases were not due to increased activity—the animals displayed an overall 15 percent decrease in movement during those same time periods.

In addition to its impact on metabolism, the two compounds also affected the animals’ activity during periods of light and darkness, suggesting that this class of compound may be useful for the treatment of sleep disorders, including the common problem of jet lag.

The first authors of the study, “Regulation of Circadian Behavior and Metabolism by Synthetic REV‐ERB Agonists,” are Laura A. Solt and Yongjun Wang of Scripps Research. Other authors include Subhashis Banerjee, Travis Hughes, Douglas J. Kojetin, Thomas Lundasen, Youseung Shin, Jin Liu, Michael D. Cameron, Romain Noel, Andrew A. Butler, and Theodore M. Kamenecka of Scripps Research; and Seung Hee Yoo and Joseph S. Takahashi of the Howard Hughes Medical Institute and University of Texas Southwestern Medical Center.