The researchers from the Medical University of Graz, the study reveals that non-invasive liquid biopsy can identify whether metastasis or recurrence of prostate cancer, lower the cost of this detection method, more suitable for the majority of the health care system. Prostate cancer genomics from plasma DNA separation, behave as chromosomal abnormal copy of the special area.
In the text, researchers said, even those hormone therapy-resistant prostate cancer patients to distinguish between hormone resistant prostate cancer is a common form of men with metastatic prostate cancer.
Prostate cancer is one of the common cancers a year in Europe alone there are 2.6 million men have been diagnosed with the disease. PSA testing in the early detection of prostate cancer, despite the use of appropriate therapy treatment, however, still some male cancer recurrence or cancer metastasis.
Still need to continue to detect cancer metastasis biopsy, the research team reported in the paper, they in a minimally invasive way to detect cancer recurrence. Use genome-wide analysis of plasma DNA technology, combined with the prostate cancer gene targeting sequencing technology, the researchers found that the presence of abnormal copy number of a special sequence of the prostate cancer, despite the abnormal sites is relatively small, including the sequence NCOA2 PHLPP1 and TMPRSS2-ERG copy number of errors.
There are slight differences in each patient cancer characteristics, however, no response of cancer patients in the castration therapy showed the increase of the androgen receptor gene copy number.
The researcher Jochen Geigl, and Professor Michael Speicher, who led the research, the liquid biopsy technology development and the performance of the universality and low response will become a traditional biopsy technology makes genetic testing, they said. Through the test from the more genetic information will help researchers to develop new types of targeted therapies, especially for those of castration therapy resistant prostate cancer, but also can be applied to the development of individualized therapy.
Genome Medicine 2013, 5:30 doi:10.1186/gm434
Tumor associated copy number changes in the circulation of patients with prostate cancer identified through whole-genome sequencing
Ellen Heitzer, Peter Ulz, Jelena Belic, Stefan Gutschi, Franz Quehenberger, Katja Fischereder, Theresa Benezeder, Martina Auer, Carina Pischler, Sebastian Mannweiler, Martin Pichler, Florian Eisner, Martin Haeusler,Sabine Riethdorf, Klaus Pantel, Hellmut Samonigg, Gerald Hoefler, Herbert Augustin, Jochen B Geigl and Michael R Speicher
Patients with prostate cancer may present with metastatic or recurrent disease despite initial curative treatment. The propensity of metastatic prostate cancer to spread to the bone has limited repeated sampling of tumor deposits. Hence, considerably less is understood about this lethal metastatic disease, as it is not commonly studied. Here we explored whole-genome sequencing of plasma DNA to scan the tumor genomes of these patients noninvasively.
We wanted to make whole-genome analysis from plasma DNA amenable to clinical routine applications and developed an approach based on a benchtop high-throughput platform, i.e. Illuminas MiSeq instrument. We performed whole-genome sequencing from plasma at a shallow sequencing depth to establish a genome-wide copy number profile of the tumor at low costs within 2 days. In parallel, we sequenced a panel of 55 high-interest genes and 38 introns with frequent fusion breakpoints such as the TMPRSS2-ERG fusion with high coverage. After intensive testing of our approach with samples from 25 individuals without cancer we analyzed 13 plasma samples derived from 5 patients with castration resistant (CRPC) and 4 patients with castration sensitive prostate cancer (CSPC).
The genome-wide profiling in the plasma of our patients revealed multiple copy number aberrations including those previously reported in prostate tumors, such as losses in 8p and gains in 8q. High-level copy number gains in the AR locus were observed in patients with CRPC but not with CSPC disease. We identified the TMPRSS2-ERG rearrangement associated 3-Mbp deletion on chromosome 21 and found corresponding fusion plasma fragments in these cases. In an index case multiregional sequencing of the primary tumor identified different copy number changes in each sector, suggesting multifocal disease. Our plasma analyses of this index case, performed 13 years after resection of the primary tumor, revealed novel chromosomal rearrangements, which were stable in serial plasma analyses over a 9 months period, which is consistent with the presence of one metastatic clone.
The genomic landscape of prostate cancer can be established by non-invasive means from plasma DNA. Our approach provides specific genomic signatures within 2 days which may therefore serve as "liquid biopsy".
A new treatment of insomnia can promote sleep but will not impair cognitive – impairs cognitive hypnotics like zolpidem (Ambien) and eszopiclone (Lunesta) standard, a common side effect.
10-15% of adults suffer insomnia, they have one-third of the people because of the sleep disorder and medication. Most of these drugs are prescription drugs like zolpidem (Ambien) and eszopiclone (Lunesta). These drugs by acting on the GABA receptor system in most patients to induce sleep; GABA is the major inhibitory neurotransmitter in the brain. However, these drugs are also associated with a number of side effects, including impaired learning, memory and attention span. Jason Uslaner MERCK together a group of scientists has developed a new sleep-promoting drugs called DORA-22, the drug may be less disrupted brain function. The study, published in the April 3 issue of ‘Science Translational Medicine ‘.
Researchers in rats and rhesus monkeys with different doses of DORA-22 with three other anti-insomnia drugs compare and test their impact on cognition.
The team found that these test animals shortly after taking DORA-22 learning and attention tasks completed and they are taking some kind of placebo effect. The drug seems to promote sleep without causing significant learning or attention damage in rodents and nonhuman primates.
DORA-22 by acting on orexin function; the orexin brain called molecules released by special nerve cells in the lateral hypothalamus part. Orexin is important to help people stay sober. Orexin help induce sleep but does not inhibit the activity of an important role in learning and memory in the brain region of the gene as a target.
These findings indicate that DORA-22 may be a better drug to the treatment of sleep disorders.
Sci Transl Med 3 April 2013:
Vol. 5, Issue 179, p. 179ra44
Sci. Transl. Med. DOI: 10.1126/scitranslmed.3005213
Orexin Receptor Antagonists Differ from Standard Sleep Drugs by Promoting Sleep at Doses That Do Not Disrupt Cognition
Jason M. Uslaner*, Spencer J. Tye, Donnie M. Eddins, Xiaohai Wang, Steven V. Fox, Alan T. Savitz, Jacquelyn Binns, Christopher E. Cannon, Susan L. Garson, Lihang Yao, Robert Hodgson, Joanne Stevens, Mark R. Bowlby, Pamela L. Tannenbaum, Joseph Brunner, Terrence P. Mcdonald, Anthony L. Gotter, Scott D. Kuduk, Paul J. Coleman, Christopher J. Winrow and John J. Renger
Current treatments for insomnia, such as zolpidem (Ambien) and eszopiclone (Lunesta), are γ-aminobutyric acid type A (GABAA)–positive allosteric modulators that carry a number of side effects including the potential to disrupt cognition. In an effort to develop better tolerated medicines, we have identified dual orexin 1 and 2 receptor antagonists (DORAs), which promote sleep in preclinical animal models and humans. We compare the effects of orally administered eszopiclone, zolpidem, and diazepam to the dual orexin receptor antagonist DORA-22 on sleep and the novel object recognition test in rat, and on sleep and two cognition tests (delayed match to sample and serial choice reaction time) in the rhesus monkey. Each compound’s minimal dose that promoted sleep versus the minimal dose that exerted deficits in these cognitive tests was determined, and a therapeutic margin was established. We found that DORA-22 has a wider therapeutic margin for sleep versus cognitive impairment in rat and rhesus monkey compared to the other compounds tested. These data were further supported with the demonstration of a wider therapeutic margin for DORA-22 compared to the other compounds on sleep versus the expression of hippocampal activity–regulated cytoskeletal-associated protein (Arc), an immediate-early gene product involved in synaptic plasticity. These findings suggest that DORAs might provide an effective treatment for insomnia with a greater therapeutic margin for sleep versus cognitive disturbances compared to the GABAA-positive allosteric modulators currently in use.
British researchers said in a report published in the journal "Science", they use a special 3D printer to print out material similar to the biological tissue, this outcome expected future applications in the medical field.
This report is published jointly by Professor Hagan Bayley of the University of Oxford and colleagues. According to reports, they take advantage of the the 3D printer hierarchical profuse droplets of lipid film wrapped, these droplets form a mesh structure, constitute a special new material.
The researchers say, to print out the material texture with brain and adipose tissue similar folding action can make a similar muscle-like activities, with work like neurons as the communication network structure can be used to repair or enhance the failure of the organ. Synthetic materials, it also avoids the problems caused by some the way manufacturing living tissue with stem cells.
The researchers also said that conventional 3D printers can not print this new material, experiment, they used a special 3D printer, this printer ejected droplet diameter of approximately 50 microns, 5 living cells so but I believe will be able to reduce the size of the droplets.
In recent years, 3D printing technology rapid development, from engineering to aerospace, from education to health care, application more widely. In February of this year, Cornell University researchers had reported that They use cells from ears of cattle3Dprinters to print out the artificial ear.
Science 5 April 2013:
Vol. 340 no. 6128 pp. 48-52
A Tissue-Like Printed Material
Gabriel Villar, Alexander D. Graham, Hagan Bayley
Living cells communicate and cooperate to produce the emergent properties of tissues. Synthetic mimics of cells, such as liposomes, are typically incapable of cooperation and therefore cannot readily display sophisticated collective behavior. We printed tens of thousands of picoliter aqueous droplets that become joined by single lipid bilayers to form a cohesive material with cooperating compartments. Three-dimensional structures can be built with heterologous droplets in software-defined arrangements. The droplet networks can be functionalized with membrane proteins; for example, to allow rapid electrical communication along a specific path. The networks can also be programmed by osmolarity gradients to fold into otherwise unattainable designed structures. Printed droplet networks might be interfaced with tissues, used as tissue engineering substrates, or developed as mimics of living tissue.
A study reported in the journal Nature Animal experiments have shown that cocaine addiction and related to the specific area of the brain neuronal activity is weak,stimulation of this area can help reduce dependence on cocaine. This achievement provides a guideline for the development of drug new method.
United States national drug Institute researchers report that they found a regional neuronal activity in the prefrontal cortex in these mice brains obviously weak study on the cocaine addiction mice brain. Previous studies have found that the ability to control the corresponding region of the human brain and behavior related to the area damaged or defective easier for cocaine addiction, is also more difficult to kick the habit.
In experiments, the researchers used up genetic techniques to stimulate this area of the brain of the mice in the "drug addicts" and found that these mice for cocaine decreased. Contrary, if the inhibition of the activity of neurons in this region, mice showed signs of addiction enhanced. The optogenetics technical combination of light with genetic engineering, can change the activity of nerve cells.
The researchers said the results show that, the anterior cerebral neuronal activity in the prefrontal cortex specific area with cocaine addiction is closely related element scan effectively improve the ability of the control of drug addiction by stimulating nerves in the region, which will contribute to the development new therapies to help people to kick the habit.
Nature (2013) doi:10.1038/nature12024
Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking
Billy T. Chen, Hau-Jie Yau, Christina Hatch, Ikue Kusumoto-Yoshida, Saemi L. Cho, F. Woodward Hopf & Antonello Bonci
Loss of control over harmful drug seeking is one of the most intractable aspects of addiction, as human substance abusers continue to pursue drugs despite incurring significant negative consequences. Human studies have suggested that deficits in prefrontal cortical function and consequential loss of inhibitory control could be crucial in promoting compulsive drug use. However, it remains unknown whether chronic drug use compromises cortical activity and, equally important, whether this deficit promotes compulsive cocaine seeking. Here we use a rat model of compulsive drug seeking in which cocaine seeking persists in a subgroup of rats despite delivery of noxious foot shocks. We show that prolonged cocaine self-administration decreases ex vivo intrinsic excitability of deep-layer pyramidal neurons in the prelimbic cortex, which was significantly more pronounced in compulsive drug-seeking animals. Furthermore, compensating for hypoactive prelimbic cortex neurons with in vivo optogenetic prelimbic cortex stimulation significantly prevented compulsive cocaine seeking, whereas optogenetic prelimbic cortex inhibition significantly increased compulsive cocaine seeking. Our results show a marked reduction in prelimbic cortex excitability in compulsive cocaine-seeking rats, and that in vivo optogenetic prelimbic cortex stimulation decreased compulsive drug-seeking behaviours. Thus, targeted stimulation of the prefrontal cortex could serve as a promising therapy for treating compulsive drug use.
A new study from the University of Maryland School of Medicine showed that depression is caused due to the ability of brain cells to communicate with each other disorders. This study indicates that a major shift in the understanding of the etiology and treatment of depression. The study, published in the latest of the "natural – Neuroscience" (Nature Neuroscience) .
The researchers did not focus on the level of serotonin in the brain and other hormone-like compounds, but found that the the excitatory signal propagation in the depression between cells become abnormal. The leadership of this study is Dr. Scott M. Thompson, a professor of the University of Maryland School of Medicine, Department of Physiology.
10 people in the United States, according to the U.S. Centers for Disease Control and Prevention (CDC) in 2005-2008, one person treated for depression, may produce more twice the number of female depression than men. The most commonly used antidepressant drugs, such as Prozac (Prozac), the left Zoloft and Celexa, brain cells by blocking absorption of serotonin (also known as 5 – HT), resulting in brain The concentration increase to play a role. Unfortunately, these drugs are effective only for the half of the patients. Some patients with depression feel better due to increased serotonin, over the past 50 years that the causes of depression must be due to inadequate levels of serotonin. Posed a challenge to this long-standing interpretation of a new study of the University of Maryland.
University of Maryland, Deputy Head of Medical Affairs, Dr. E. Albert Reece, dean and professor of the University of Maryland School of Medicine, said: "Dr. Thompson innovative research has the potential to change the field of psychiatric medicine, and change our understanding of depression and other mental illness caused serious consequences public health problem at the University of Maryland, in this type of cutting-edge science to work, hoping to be obtained in the laboratory findings can influence clinical medical practice. "
The involvement of adults in the United States for more than a quarter of a stage in the life of depression. According to the World Health Organization estimated that by 2020 depression will become the second leading cause of disability in the world. The most important risk factor for depression is suicide, resulting in the death of double murder, is the third largest cause of death of young people aged 15-24.
A major new study found that: confirmed that serotonin has a previously unknown ability to enhance the communication between brain cells. "It’s like a noisy cocktail party in front of your companions speak loudly, serotonin amplifies excitatory interactions important for mood and cognitive function in the region of the brain, just like to help ensure that the neurons of between some of the crucial dialogue can be heard, then we want to know is that the impact caused by serotonin role in the therapeutic effects of drugs such as Prozac? "Thompson said.
In order to understand the brain of patients with depression may be anything unusual occurred, as well as mechanisms to improve serum known as possible to relieve symptoms, the research team tested repeatedly in the brain of rats and mice under the various mild pressure conditions.
The researchers based on animal loss preferences, under normal circumstances it something pleasant to conclude that they become depressed. For example, normal animals choose to drink white water or sugar water, they would be strongly inclined to the sugar solution. And repeated contact pressure of the animals, but the loss of a preference for sugar water, suggesting that they are no longer considered rewarding. Depression-like behavior effectively simulate a sign of human depression to: interest deletion. Patients no longer because of the pleasure of a good meal or a good movie, and the love of friends and family, as well as countless other daily interactions and feeling rewarded.
The activity of rat brain cells in normal rats and pressure comparison, the researchers found that the pressure for the depression of the brain serotonin levels, there is no impact, but excitatory connections in a significantly different way to make the corresponding serotonin. When antidepressants in the treatment of these pressures animal, these changes can be reversed, they return to normal behavior.
"Brain in depression, serotonin seems to be trying to enlarge the cocktail party dialogue, but the signal is still not through," Thompson said. The ability of specific engineered mice generated by the Johns Hopkins University School of Medicine collaborators, the study also reveals enhanced excitatory synaptic serotonin is a necessary condition for the role of antidepressants.
Has continued to improve the communication between the brain cells is considered to be one of the important process as the basis of memory and learning. The research team’s results show that the model of depression, the excitatory brain function changes may explain the depression patients often in concentration, memory details or make difficult decisions. In addition, the study found that antidepressant compounds to find new and better drugs raise serotonin drugs should be connected to the enhanced excitability shift.
"Although there is a lot of work to be done, we believe the excitatory synaptic failure for the origin of the depression is extremely important. Restore normal communication in the brain, it is clear the mechanism of serotonin play a role in the successful treatment of patients, but also to alleviate the damage The key of the disease symptoms, "Dr. Thompson explained.
Nature Neuroscience 16,464–472(2013)
Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression
Xiang Cai, Angy J Kallarackal, Mark D Kvarta, Sasha Goluskin, Kaitlin Gaylor, Aileen M Bailey, Hey-Kyoung Lee, Richard L Huganir & Scott M Thompson
The causes of major depression remain unknown. Antidepressants elevate concentrations of monoamines, particularly serotonin, but it remains uncertain which downstream events are critical to their therapeutic effects. We found that endogenous serotonin selectively potentiated excitatory synapses formed by the temporoammonic pathway with CA1 pyramidal cells via activation of serotonin receptors (5-HT1BRs), without affecting nearby Schaffer collateral synapses. This potentiation was expressed postsynaptically by AMPA-type glutamate receptors and required calmodulin-dependent protein kinase–mediated phosphorylation of GluA1 subunits. Because they share common expression mechanisms, long-term potentiation and serotonin-induced potentiation occluded each other. Long-term consolidation of spatial learning, a function of temporoammonic-CA1 synapses, was enhanced by 5-HT1BR antagonists. Serotonin-induced potentiation was quantitatively and qualitatively altered in a rat model of depression, restored by chronic antidepressants, and required for the ability of chronic antidepressants to reverse stress-induced anhedonia. Changes in serotonin-mediated potentiation, and its recovery by antidepressants, implicate excitatory synapses as a locus of plasticity in depression.
U.S. researchers report that they first "functional cure" for HIV infection in infants by antiretroviral therapy.
Researchers of the Johns Hopkins Children’s Medical Center, University of Mississippi and other institutions, held in Atlanta, USA, in 2013, retroviruses and opportunistic infections, the General Assembly, "the report said, they select the one two years ago by the mother child transmission of HIV-infected baby girl for the treatment of the object. In the 30 hours after the baby was born, the researchers their combined antiretroviral therapy.
In testing, the number of significantly decreasing after treatment of HIV in the blood of the baby girl born 29 days after the body of the AIDS virus has not detected. Researchers in the next 18 months to continue her antiretroviral therapy, stop treatment and 10 months after the discovery, the body of HIV antibodies is still negative, the AIDS virus is not found in routine blood test.
The researchers said: "neonatal antiretroviral treatment can prevent internal concealment of the HIV-infected host cells, the therapy can clear suppression of the virus, in the case of non-life treatment to achieve a ‘functional cure’."
"Functional cure" refers to the HIV infected individuals were completely inhibited, the normal immune function, even if not treated by a conventional method, it is difficult to detect a virus in the blood of children.
The researchers said that the eradication of HIV, that "radical cure" AIDS is currently difficult to achieve. Medication for HIV infection in infants by now, the general began its between 3-4 months after birth, so as soon as possible, accurate antiretroviral treatment of infants infected with the AIDS virus is significant.
According to reports, the world is currently about 2.5 million babies infected with the AIDS virus, HIV mother-to-child transmission of about 1,700 new cases a day.
A Japanese research team found that the genetic manipulation of the cancer stem cells may be more likely to play a role in the chemotherapy drugs to kill cancer cells. This discovery or to promote the development of a cure for cancer treatment.
Tumor stem cells in the body is almost non-proliferation "hibernation". Although chemotherapy drugs to curb the proliferation of tumor cells, stem cells are difficult to play a role. Even after chemotherapy, the tumor seems to have disappeared, but the small amount of residual stem cells can lead to cancer recurrence and metastasis.
Shoichiro Takeishi, a professor at Kyushu University, Japan, led the research team found that cancer stem cells called "Fbxw7" protein to curb cell division. Their suffering from chronic myelogenous leukemia in mice, the genetic manipulation, so that the tumor stem cells can not be re-manufacturing of this protein. Since then, the researchers gave the mice taking the chemotherapy drug Gleevec, 35 days after the administration no longer.
The study found that, under normal circumstances, suffering from leukemia mice after 60 days there will be a recurrence rate of 90%, but can not manufacture "Fbxw7" protein in mice recurrence rate of only about 20%. The research team judged to have died of cancer stem cells.
Cancer Cell, Volume 23, Issue 3, 347-361, 18 March 2013
Ablation of Fbxw7 Eliminates Leukemia-Initiating Cells by Preventing Quiescence
Shoichiro Takeishi,Akinobu Matsumoto,Ichiro Onoyama,Kazuhito Naka,Atsushi Hirao,Keiichi I. Nakayama
Imatinib eradicates dividing progenitor cells of chronic myeloid leukemia (CML) but does not effectively target nondividing leukemia-initiating cells (LICs); thus, the disease often relapse after its discontinuation. We now show that Fbxw7 plays a pivotal role in maintenance of quiescence in LICs of CML by reducing the level of c-Myc. Abrogation of quiescence in LICs by Fbxw7 ablation increased their sensitivity to imatinib, and the combination of Fbxw7 ablation with imatinib treatment resulted in a greater depletion of LICs than of normal hematopoietic stem cells in mice. Purging of LICs by targeting Fbxw7 to interrupt their quiescence and subsequent treatment with imatinib may thus provide the basis for a promising therapeutic approach to CML.
Recently a new study completed by the University of California, Los Angeles (UCLA), and the California Institute of Technology scientists genetically engineered immune cells may help to improve the treatment of melanoma, melanoma is a deadly form of skin cancer to.
The study is published in the March 21 Cancer Discovery magazine, renewable Medicine and Stem Cell Institute, James Heath and the University of California, Los Angeles Jonsson Comprehensive Cancer Center members, led by the University of California, Los Angeles, Eli and Edythe Eli. Mr. Heath is a professor of the UCLA molecular and medical pharmacology.
Melanoma patient’s own immune cells to T cells is very important to the treatment of melanoma treatment. Cells in the laboratory by genetically modified so that when these T cells are re-introduced into the patient’s blood, they specifically attack melanoma. In early clinical trial results show that this treatment in many patients can lead to significant tumor shrinkage, but the positive impact is often short-lived.
University of California, Los Angeles (UCLA), and the California Institute of Technology researchers found that genetically modified T cells are able to treat patients, but its efficacy will disappear within two to three weeks. Surprisingly,however, once the genetically engineered cells are no longer valid, and a new set of non-engineered T cells in the patient’s body, a similar tumor-killing effects, and even longer duration.
Published Online First March 21, 2013; doi:10.1158/2159-8290.CD-12-0383
Multifunctional T-cell Analyses to Study Response and Progression in Adoptive Cell Transfer Immunotherapy
Chao Ma, Ann F. Cheung, Thinle Chodon, Richard C. Koya, Zhongqi Wu, Charles Ng, Earl Avramis, Alistair J. Cochran, Owen N. Witte, David Baltimore, Bartosz Chmielowski, James S. Economou, Begonya Comin-Anduix, Antoni Ribas and James R. Heath
Adoptive cell transfer (ACT) of genetically engineered T cells expressing cancer-specific T-cell receptors (TCR) is a promising cancer treatment. Here, we investigate the in vivofunctional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. The analyses included evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell subpopulations, as well as the enumeration of T cells with TCR antigen specificity for 36 melanoma antigens. These analyses revealed the coordinated functional dynamics of the adoptively transferred, as well as endogenous, T cells, and the importance of highly functional T cells in dominating the antitumor immune response. This study highlights the need to develop approaches to maintaining antitumor T-cell functionality with the aim of increasing the long-term efficacy of TCR-engineered ACT immunotherapy.
A study reported that, for five consecutive days lack of sleep beyond energy demand will increase in food intake and lead to weight gain. Kenneth P. Wright, Jr. and his colleagues on the five days of lack of sleep on the total daily energy expenditure and total intake of 16 adults were quantified. The authors found that the subjects were allowed to sleep up to nine hours, when the subjects were allowed to sleep for up to five hours, the average daily energy expenditure increased by about5%. Food intake in these subjects is also a lack of sleep increased, leading to weight gain. Leptin, gastrin hormone, and the issue of excessive food intake signal YY-peptide levels changed subjects or excessive eating.
During the lack of sleep, the subjects ate a small breakfast, but after dinner to eat rich in carbohydrates, protein and fiber snacks and increased caloric intake. When subjects from lack of sleep to sleep enough, they reduce the calorie intake is to reduce the intake of calories from fat and carbohydrates, and reduce weight. Unlike male subjects, female subjects during adequate sleep to maintain their weight, but when they get enough sleep showed a the dietary restrictions reduction and weight increase. The authors said the study proved that lack of sleep may lead to weight gain mechanism.
doi:10.1073/pnas.1216951110 PNAS March 11, 2013 201216951
Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain
Rachel R. Markwald, Edward L. Melanson, Mark R. Smith, Janine Higgins, Leigh Perreault,
Robert H. Eckel, and Kenneth P. Wright, Jr
Insufficient sleep is associated with obesity, yet little is known about how repeated nights of insufficient sleep influence energy expenditure and balance. We studied 16 adults in a 14- to 15-d-long inpatient study and quantified effects of 5 d of insufficient sleep, equivalent to a work week, on energy expenditure and energy intake compared with adequate sleep. We found that insufficient sleep increased total daily energy expenditure by ∼5%; however, energy intake—especially at night after dinner—was in excess of energy needed to maintain energy balance. Insufficient sleep led to 0.82 ± 0.47 kg (±SD) weight gain despite changes in hunger and satiety hormones ghrelin and leptin, and peptide YY, which signaled excess energy stores. Insufficient sleep delayed circadian melatonin phase and also led to an earlier circadian phase of wake time. Sex differences showed women, not men, maintained weight during adequate sleep, whereas insufficient sleep reduced dietary restraint and led to weight gain in women. Our findings suggest that increased food intake during insufficient sleep is a physiological adaptation to provide energy needed to sustain additional wakefulness; yet when food is easily accessible, intake surpasses that needed. We also found that transitioning from an insufficient to adequate/recovery sleep schedule decreased energy intake, especially of fats and carbohydrates, and led to −0.03 ± 0.50 kg weight loss. These findings provide evidence that sleep plays a key role in energy metabolism. Importantly, they demonstrate physiological and behavioral mechanisms by which insufficient sleep may contribute to overweight and obesity.
The Japanese Ministry of Health, Labor and Welfare research team report in Proceedings of the 25th European Diabetes Association "Diabetes", large-scale epidemiological survey found that diabetics about one hour of exercise per day, the risk of death and brain of stroke risk is reduced by about half.
The researchers tracked these patients for up to eight years, according to the amount of exercise the patients were divided into several groups, and the incidence and mortality of their physical activity and stroke, myocardial infarction complications.Which exercise most per day walk to the faster speed of six kilometers per hour for about 70 minutes, or the equivalent of swimming 30-40 minutes, but at least one group, in addition to the work and activities of daily living, almost no movement.
The results found that exercise up to a group of patients with myocardial infarction and other complications and death risk is to exercise at least a group of approximately 47%, the risk of suffering from stroke only about 57% of the latter.
Published online before print February 12, 2013, doi: 10.2337/dc12-0958
Predicting Macro- and Microvascular Complications in Type 2 Diabetes
The Japan Diabetes Complications Study/the Japanese Elderly Diabetes Intervention Trial risk engine
Shiro Tanaka, PHD, Sachiko Tanaka, PHD, Satoshi Iimuro, MD, PHD, Hidetoshi Yamashita, MD, PHD, Shigehiro Katayama, MD, PHD5, Yasuo Akanuma, MD, PHD6, Nobuhiro Yamada, MD, PHD7, Atsushi Araki, MD, PHD8, Hideki Ito, MD, PHD8, Hirohito Sone, MD, PHD7, Yasuo Ohashi, PHD
OBJECTIVE To develop and validate a risk engine that calculates the risks of macro- and microvascular complications in type 2 diabetes.
RESEARCH DESIGN AND METHODS We analyzed pooled data from two clinical trials on 1,748 Japanese type 2 diabetic patients without diabetes complications other than mild diabetic retinopathy with a median follow-up of 7.2 years. End points were coronary heart disease (CHD), stroke, noncardiovascular mortality, overt nephropathy defined by persistent proteinuria, and progression of retinopathy. We fit a multistate Cox regression model to derive an algorithm for prediction. The predictive accuracy of the calculated 5-year risks was cross-validated.
RESULTS Sex, age, HbA1c, years after diagnosis, BMI, systolic blood pressure, non-HDL cholesterol, albumin-to-creatinine ratio, atrial fibrillation, current smoker, and leisure-time physical activity were risk factors for macro- and microvascular complications and were incorporated into the risk engine. The observed-to-predicted (O/P) ratios for each event were between 0.93 and 1.08, and Hosmer-Lemeshow tests showed no significant deviations between observed and predicted events. In contrast, the UK Prospective Diabetes Study (UKPDS) risk engine overestimated CHD risk (O/P ratios: 0.30 for CHD and 0.72 for stroke). C statistics in our Japanese patients were high for CHD, noncardiovascular mortality, and overt nephropathy (0.725, 0.696, and 0.767) but moderate for stroke and progression of retinopathy (0.636 and 0.614). By combining macro- and microvascular risks, the classification of low- and high-risk patients was improved by a net reclassification improvement of 5.7% (P = 0.02).
CONCLUSIONS The risk engine accurately predicts macro- and microvascular complications and would provide helpful information in risk classification and health economic simulations.