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Sample records for deprivation therapy t-score

  1. Sleep deprivation therapy.

    PubMed

    Svestka, Jaromir

    2008-11-01

    Sleep deprivation is a useful therapeutic option in the treatment of depressive disorders, especially in pharmacoresistant disorders. Its therapeutic efficacy in other indications has not, however, been confirmed. According to current knowledge, application of sleep therapy requires concomitant therapy to prevent early relapses of depression. Total sleep deprivation is the classic variant of its clinical use. Partial sleep deprivation has a somewhat less pronounced antidepressant effect, and the duration of sleep deprivation rather than application timing determines its therapeutic effect. The most reliable predictors of sleep deprivation efficacy are marked diurnal fluctuations of depressive mood, patient locomotor activity, and limbic hyperactivity in the central nervous system. The mechanism of the antidepressant effect of sleep deprivation remains unknown. PMID:19029872

  2. Sleep deprivation therapy for depression.

    PubMed

    Dallaspezia, Sara; Benedetti, Francesco

    2015-01-01

    Sleep deprivation (SD) is the most widely documented rapid-onset antidepressant therapy, targeting the broadly defined depressive syndrome. Although SD responses are transient, its effects can be sustained by concomitant medications (e.g., selective serotonin reuptake inhibitors and lithium) and circadian-related interventions (e.g., bright light and sleep phase advance). Thus, considering its safety, this technique can now be considered among the first-line antidepressant treatment strategies for patients affected by mood disorders. SD is a complex intervention and it should be considered multi-target in nature. Thus, the mechanisms explaining its antidepressant effect can be looked for on many levels, involving not only monoaminergic mechanisms but also sleep homeostatic and circadian mechanisms, glutamatergic mechanisms and synaptic plasticity. PMID:25549913

  3. Intermittent versus continuous androgen deprivation therapy.

    PubMed

    Higano, Celestia S

    2014-05-01

    Androgen deprivation therapy (ADT) has been the standard of care for metastatic prostate cancer for decades; however, the choice of continuous or intermittent administration is a matter of debate. Two large phase III trials have reported results comparing these 2 forms of ADT administration. The National Cancer Institute of Canada (NCIC) PR-7 trial studied men with an increasing prostate-specific antigen (PSA) level and no evidence of metastatic disease after definitive or salvage radiation therapy and radical prostatectomy. The Southwest Oncology Group 9346 trial studied men with newly diagnosed hormone-sensitive metastatic disease. The primary end point in both trials was overall survival with a noninferiority design. The NCIC trial showed that the overall survival in men treated with intermittent ADT was not inferior to that of men treated with continuous ADT, but the SWOG trial was inconclusive regarding noninferiority. Certain domains of quality of life were better in the intermittent arms of both trials. If using ADT in the setting of biochemical relapse, intermittent ADT should be strongly considered over continuous ADT, except perhaps in patients with Gleason score of 8 or higher. In men with metastatic disease, continuous ADT remains the standard of care, because the SWOG trial did not establish noninferiority of intermittent ADT with respect to survival. However, for those with significant side effects from ADT, establishing the risk group, as determined by PSA value after 7 months of ADT or the presence of pain at diagnosis, may help guide the choice of intermittent versus continuous ADT in men with metastatic disease. PMID:24812139

  4. Androgen deprivation therapy (castration therapy) and pedophilia: What's new.

    PubMed

    Silvani, Mauro; Mondaini, Nicola; Zucchi, Alessandro

    2015-09-01

    Andrology is a constantly evolving discipline, embracing social problems like pedophilia and its pharmacological treatment. With regard to chemical castration, the andrologist may perform an important role as part of a team of specialists. At present, no knowledge is available regarding hormonal, chromosomal or genetic alterations involved in pedophilia. International legislation primarily aims to defend childhood, but does not provide for compulsory treatment. We reviewed international literature that, at present, only comprises a few reports on research concerning androgen deprivation. Most of these refer to the use of leuprolide acetate, rather than medroxyprogesterone and cyproterone acetate, which present a larger number of side effects. Current opinions on chemical castration for pedophilia are discordant. Some surveys confirm that therapy reduces sexual thoughts and fantasies, especially in recidivism. On the other hand, some authors report that chemical castration does not modify the pedophile's personality. In our opinion, once existing legislation has changed, andrologists could play a significant role in the selection of patients to receive androgen deprivation therapy, due in part to their knowledge about its action and side effects. PMID:26428645

  5. Risk of Diabetes among Patients Receiving Primary Androgen Deprivation Therapy for Clinically Localized Prostate Cancer

    PubMed Central

    Tsai, Huei-Ting; Keating, Nancy L.; Van Den Eeden, Stephen K.; Haque, Reina; Cassidy-Bushrow, Andrea E.; Yood, Marianne Ulcickas; Smith, Matthew R.; Potosky, Arnold L.

    2015-01-01

    Purpose Androgen deprivation therapy may increase diabetes risk. As the benefits of primary androgen deprivation therapy for localized prostate cancer are controversial, and most prostate cancer survivors are of advanced age with comorbidities, it is important to determine if primary androgen deprivation therapy increases the risk of diabetes and to determine the susceptibility factors. Materials and Methods We conducted a retrospective cohort study of 12,191 men diagnosed with incident localized prostate cancer during 1995 to 2008, age 35 to 100 years, and without diabetes or receipt of prostatectomy or radiation 1 year after diagnosis. Patients were enrolled in 1 of 3 managed health plans and followed through 2010. Primary androgen deprivation therapy was defined as androgen deprivation therapy within 1 year after diagnosis. Incident diabetes was ascertained using inpatient and outpatient diagnosis codes, diabetes medications and hemoglobin A1c values. We estimated primary androgen deprivation therapy associated diabetes risk using Cox proportional hazard models in conventional and propensity score analyses. Results Diabetes developed in 1,203 (9.9%) patients during followup (median 4.8 years) with incidence rates of 2.5 and 1.6 events per 100 person-years in the primary androgen deprivation therapy and nonprimary androgen deprivation therapy groups, respectively. Primary androgen deprivation therapy was associated with a 1.61-fold increased diabetes risk (95% CI 1.38–1.88). The number needed to harm was 29. The association was stronger in men age 70 or younger than in older men (HR 2.25 vs 1.40, p value for interaction = 0.008). Conclusions Primary androgen deprivation therapy may increase diabetes risk by 60% and should be used with caution when managing localized prostate cancer. Because of the consistent association between androgen deprivation therapy and greater diabetes risk across disease states, we recommend routine screening and lifestyle

  6. [Cardiovascular risks of androgen deprivation therapy for prostate cancer].

    PubMed

    Miller, K

    2016-05-01

    Androgen deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. It has increasingly been used in other stages of the disease as well. Besides well-known side effects caused by the lack of testosterone (impotency, osteoporosis, fatigue, loss of muscle mass), an increase of cardiovascular (CV) morbidity and mortality has recently been discussed in association with ADT. Cardiovascular side effects cannot be sufficiently explained by low testosterone levels. This review gives an overview of the recent literature, interprets the results, and offers clinical consequences. PMID:27003571

  7. Androgen deprivation therapy: progress in understanding mechanisms of resistance and optimizing androgen depletion

    PubMed Central

    Harris, William P; Mostaghel, Elahe A; Nelson, Peter S; Montgomery, Bruce

    2010-01-01

    SUMMARY Androgen deprivation therapy remains a critical component of treatment for men with advanced prostate cancer, and data supports its use in metastatic disease and in conjunction with surgery or radiation in specific settings. Alternatives to standard androgen deprivation therapy, such as intermittent androgen suppression and estrogen therapy, hold the potential to improve toxicity profiles while maintaining clinical benefit. Current androgen deprivation strategies seem to incompletely suppress androgen levels and androgen-receptor-mediated effects at the tissue level. Advances in the understanding of mechanisms that contribute to castration-resistant prostate cancer are leading to rationally designed therapies targeting androgen metabolism and the androgen receptor. The results of large trials investigating the optimization of primary androgen deprivation therapy, including evaluation of intermittent androgen suppression and estrogen patch assessment, as well as phase III studies of novel androgen synthesis inhibitors, such as abiraterone acetate, are eagerly awaited. PMID:19198621

  8. MMPI T Scores: Linear versus Normalized.

    ERIC Educational Resources Information Center

    Hsu, Louis M.

    1984-01-01

    Includes two articles regarding scoring for Minnesota Multiphasic Personality Inventory scales. Comments on the advisability of utilizing normalized T scores (Hsu), and addresses these objections from a theoretical standpoint and in the context of responses from a new reference sample (Colligan, Osborne, and Offord). (LLL)

  9. Androgen deprivation therapy for prostate cancer—review of indications in 2010

    PubMed Central

    Quon, H.; Loblaw, D.A.

    2010-01-01

    The discovery of androgen deprivation therapy (adt) has been one of the most important advances in the treatment of prostate cancer. Here, the indications for the use of adt are reviewed, together with the data supporting each indication. The settings for adt use include cytoreduction; combined adt and radiotherapy; pathologic node-positive disease; and recurrent, metastatic, or progressive prostate cancer. PMID:20882131

  10. [Combined radiation therapy and androgen deprivation in the management of prostate cancer: Where do we stand?].

    PubMed

    Bellefqih, S; Hadadi, K; Mezouri, I; Maghous, A; Marnouche, E; Andaloussi, K; Elmarjany, M; Sifat, H; Mansouri, H; Benjaafar, N

    2016-04-01

    Radiotherapy and androgen deprivation therapy play a major role in the management of prostate cancer. Indeed, radiotherapy and hormone therapy are combined in a neoadjuvant and concomitant setting for intermediate risk cancers but also in an adjuvant setting in high risk or locally advanced prostate cancer. The benefice of this association was suggested by preclinical studies and demonstrated later by several randomized trials. However, as these trials were conducted before the era of dose escalation the role of androgen deprivation therapy in this case is less clear. Moreover, as hormonal therapy can lead to a significant morbidity and a decrement in quality of life its indications must be carefully weighed especially in case of intermediate risk cancer witch represent a heterogeneous group with distinct prognostic subgroups. PMID:26969245

  11. Intensive sleep deprivation and cognitive behavioral therapy for pharmacotherapy refractory insomnia in a hospitalized patient.

    PubMed

    Breitstein, Joshua; Penix, Brandon; Roth, Bernard J; Baxter, Tristin; Mysliwiec, Vincent

    2014-06-15

    The case of a 59-year-old woman psychiatrically hospitalized with comorbid insomnia, suicidal ideation, and generalized anxiety disorder is presented. Pharmacologic therapies were unsuccessful for treating insomnia prior to and during hospitalization. Intensive sleep deprivation was initiated for 40 consecutive hours followed by a recovery sleep period of 8 hours. Traditional components of cognitive behavioral therapy for insomnia (CBTi), sleep restriction, and stimulus control therapies, were initiated on the ward. After two consecutive nights with improved sleep, anxiety, and absence of suicidal ideation, the patient was discharged. She was followed in the sleep clinic for two months engaging in CBTi. Treatment resulted in substantial improvement in her insomnia, daytime sleepiness, and anxiety about sleep. Sleep deprivation regimens followed by a restricted sleep recovery period have shown antidepressant effects in depressed patients. Similar treatment protocols have not been investigated in patients with pharmacotherapy refractory insomnia and generalized anxiety disorder. PMID:24932151

  12. Androgen Deprivation Therapy and Secondary Hormone Therapy in the Management of Hormone-sensitive and Castration-resistant Prostate Cancer.

    PubMed

    Saad, Fred; Fizazi, Karim

    2015-11-01

    Androgen deprivation therapy (ADT) is the standard of care for patients with metastatic prostate cancer (mPC). However, nearly all patients with mPC progress to castration-resistant PC (CRPC). Arrays of treatments, including secondary hormonal therapies, are available for the treatment of mPC and CRPC, which show efficacy when administered with ADT. Continuation of ADT is recommended for CRPC treatment as therapies are added. New secondary hormonal therapies include abiraterone, targeting the CYP17 enzyme family, and enzalutamide, an androgen receptor inhibitor with heightened binding specificity. The optimal decision-making process for CRPC treatment option remains unclear, pending further research and experience. PMID:26282624

  13. Influence of Age on Incident Diabetes and Cardiovascular Disease in Prostate Cancer Survivors Receiving Androgen Deprivation Therapy

    PubMed Central

    Morgans, Alicia K.; Fan, Kang-Hsien; Koyama, Tatsuki; Albertsen, Peter C.; Goodman, Michael; Hamilton, Ann S.; Hoffman, Richard M.; Stanford, Janet L.; Stroup, Antoinette M.; Resnick, Matthew J.; Barocas, Daniel A.; Penson, David F.

    2015-01-01

    Purpose Observational data suggest that androgen deprivation therapy increases the risk of diabetes and cardiovascular disease. Using data from the population based PCOS we evaluated whether age at diagnosis and comorbidity impact the association of androgen deprivation therapy with incident diabetes and cardiovascular disease. Materials and Methods We identified men with nonmetastatic prostate cancer diagnosed from 1994 to 1995 who were followed through 2009 to 2010. We used multivariable logistic regression models to assess the relationship of androgen deprivation therapy exposure (2 or fewer years, greater than 2 years or none) with incident diabetes and cardiovascular disease, adjusting for age at diagnosis, race, stage and comorbidity. Results Of 3,526 eligible study participants 2,985 without diabetes and 3,112 without cardiovascular disease comprised the cohorts at risk. Androgen deprivation therapy was not associated with an increased risk of diabetes or cardiovascular disease in men diagnosed with prostate cancer before age 70 years. Prolonged androgen deprivation therapy and increasing age at diagnosis in older men was associated with an increased risk of diabetes (at age 76 years OR 2.1, 95% CI 1.0–4.4) and cardiovascular disease (at age 74 years OR 1.9, 95% CI 1.0–3.5). Men with comorbidities were at greater risk for diabetes (OR 4.3, 95% CI 2.3–7.9) and cardiovascular disease (OR 8.1, 95% CI 4.3–15.5) than men without comorbidities. Conclusions Prolonged androgen deprivation therapy exposure increases the risk of cardiovascular disease and diabetes in men diagnosed with prostate cancer who are older than approximately 75 years, especially those with other comorbidities. Older men who receive prolonged androgen deprivation therapy should be closely monitored for diabetes and cardiovascular disease. PMID:25451829

  14. Baseline Serum Testosterone in Men Treated With Androgen Deprivation Therapy and Radiotherapy for Localized Prostate Cancer

    SciTech Connect

    Roach, Mack; Bae, Kyounghwa; Lawton, Colleen; Donnelly, B.J.; Grignon, David; Hanks, Gerald E.; Porter, Arthur; Lepor, Herbert; Venketesan, Varagur; Sandler, Howard

    2010-12-01

    Introduction: It is believed that men diagnosed with prostate cancer and a low baseline serum testosterone (BST) may have more aggressive disease, and it is frequently recommended they forgo testosterone replacement therapy. We used two large Phase III trials involving androgen deprivation therapy and external beam radiation therapy to assess the significance of a BST. Methods and Materials: All patients with a BST and complete data (n = 2,478) were included in this analysis and divided into four categories: 'Very Low BST' (VLBST) {<=}16.5th percentile of BST ({<=}248 ng/dL; n = 408); 'Low BST' (LBST) >16.5th percentile and {<=}33rd percentile (>248 ng/dL but {<=}314 ng/dL; n = 415); 'Average BST' (ABST) >33rd percentile and {<=}67th percentile (314-437 ng/dL; n = 845); and 'High BST' (HBST) >67th percentile (>437 ng/dL; n = 810). Outcomes included overall survival, distant metastasis, biochemical failure, and cause-specific survival. All outcomes were adjusted for the following covariates: treatment arm, BST, age (<70 vs. {>=}70), prostate-specific antigen (PSA; <10 vs. 10 {<=} PSA <20 vs. 20 {<=}), Gleason score (2-6 vs. 7 vs. 8-10); T stage (T1-T2 vs. T3-T4), and Karnofsky Performance Status (60-90 vs. 100). Results: On multivariable analysis age, Gleason score, and PSA were independently associated with an increased risk of biochemical failure, distant metastasis and a reduced cause-specific and overall survival (p < 0.05), but BST was not. Conclusions: BST does not affect outcomes in men treated with external beam radiation therapy and androgen deprivation therapy for prostate cancer.

  15. Systemic therapy for the treatment of hormone-sensitive metastatic prostate cancer: from intermittent androgen deprivation therapy to chemotherapy.

    PubMed

    Liaw, Bobby C; Shevach, Jeffrey; Oh, William K

    2015-03-01

    Treatment of advanced prostate cancer has changed considerably in recent years, but the vast majority of advances have been made in patients with metastatic castration-resistant disease. There have been relatively fewer advances in the earlier, hormonally responsive stage of metastatic disease. Since the empiric establishment of androgen deprivation therapy as first-line therapy for metastatic prostate cancer decades ago, there have been multiple studies looking at variations of suppressing testosterone, but the overall paradigm has not been strongly challenged until more recently. In particular, the dramatic results reported by the CHAARTED trial not only bring chemotherapy to an arena historically dominated solely by hormonal therapy but also stimulate renewed efforts into improving upon our management of metastatic hormone-sensitive prostate cancer. PMID:25677235

  16. Can Mathematical Models Predict the Outcomes of Prostate Cancer Patients Undergoing Intermittent Androgen Deprivation Therapy?

    NASA Astrophysics Data System (ADS)

    Everett, R. A.; Packer, A. M.; Kuang, Y.

    Androgen deprivation therapy is a common treatment for advanced or metastatic prostate cancer. Like the normal prostate, most tumors depend on androgens for proliferation and survival but often develop treatment resistance. Hormonal treatment causes many undesirable side effects which significantly decrease the quality of life for patients. Intermittently applying androgen deprivation in cycles reduces the total duration with these negative effects and may reduce selective pressure for resistance. We extend an existing model which used measurements of patient testosterone levels to accurately fit measured serum prostate specific antigen (PSA) levels. We test the model's predictive accuracy, using only a subset of the data to find parameter values. The results are compared with those of an existing piecewise linear model which does not use testosterone as an input. Since actual treatment protocol is to re-apply therapy when PSA levels recover beyond some threshold value, we develop a second method for predicting the PSA levels. Based on a small set of data from seven patients, our results showed that the piecewise linear model produced slightly more accurate results while the two predictive methods are comparable. This suggests that a simpler model may be more beneficial for a predictive use compared to a more biologically insightful model, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting. Nevertheless, both models are an important step in this direction.

  17. Can Mathematical Models Predict the Outcomes of Prostate Cancer Patients Undergoing Intermittent Androgen Deprivation Therapy?

    NASA Astrophysics Data System (ADS)

    Everett, R. A.; Packer, A. M.; Kuang, Y.

    2014-04-01

    Androgen deprivation therapy is a common treatment for advanced or metastatic prostate cancer. Like the normal prostate, most tumors depend on androgens for proliferation and survival but often develop treatment resistance. Hormonal treatment causes many undesirable side effects which significantly decrease the quality of life for patients. Intermittently applying androgen deprivation in cycles reduces the total duration with these negative effects and may reduce selective pressure for resistance. We extend an existing model which used measurements of patient testosterone levels to accurately fit measured serum prostate specific antigen (PSA) levels. We test the model's predictive accuracy, using only a subset of the data to find parameter values. The results are compared with those of an existing piecewise linear model which does not use testosterone as an input. Since actual treatment protocol is to re-apply therapy when PSA levels recover beyond some threshold value, we develop a second method for predicting the PSA levels. Based on a small set of data from seven patients, our results showed that the piecewise linear model produced slightly more accurate results while the two predictive methods are comparable. This suggests that a simpler model may be more beneficial for a predictive use compared to a more biologically insightful model, although further research is needed in this field prior to implementing mathematical models as a predictive method in a clinical setting. Nevertheless, both models are an important step in this direction.

  18. Integrating diet and exercise into care of prostate cancer patients on androgen deprivation therapy.

    PubMed

    Moyad, Mark A; Newton, Robert U; Tunn, Ulf W; Gruca, Damian

    2016-01-01

    Improved diagnosis and treatment regimens have resulted in greater longevity for men with prostate cancer. This has led to an increase in both androgen deprivation therapy (ADT) use and duration of exposure, and therefore to its associated adverse effects, such as sexual dysfunction, osteoporosis, reduced muscle mass, increased fat mass, and increased incidence of cardiovascular disease and type 2 diabetes. Given that the adverse effects of ADT are systemic, often debilitating, and difficult to treat, efforts continue in the development of new strategies for long-term management of prostate cancer. The PubMed database was searched to select trials, reviews, and meta-analyses in English using such search terms as "prostate cancer" and "androgen deprivation therapy", "cardiovascular risk", "lean body mass", "exercise", and "diet". The initial searches produced 379 articles with dates 2005 or more recent. Articles published after 2004 were favored. This review utilizes the latest data to provide a status update on the effects of exercise and diet on patients with prostate cancer, focusing on ADT-associated side effects, and it discusses the evidence for such interventions. Since the evidence of large-scale trials in patients with prostate cancer is missing, and an extrapolation of supporting data to all patient subgroups cannot be provided, individualized risk assessments remain necessary before the initiation of exercise and diet programs. Exercise, diet, and nutritional supplementation interventions have the potential to provide effective, accessible, and relatively inexpensive strategies for mitigating ADT-associated toxicities without introducing additional adverse effects. PMID:27574584

  19. Osteoporosis diagnosis in men: the T-score controversy revisited.

    PubMed

    Binkley, Neil; Adler, Robert; Bilezikian, John P

    2014-12-01

    Osteoporosis becomes common with aging in both sexes, but is often ignored in men. The 2013 International Society for Clinical Densitometry consensus conference endorsed a Caucasian female referent database for T-score calculation in men. This recommendation has generated controversy and concern. Accumulating data indicate that at the same DXA-measured body mineral density (BMD) (g/cm(2)), men and women are at approximately the same fracture risk. With this point in mind, using the same database to derive the T-score in men and women is reasonable. As a result, a greater proportion of men who sustain a fragility fracture will have T-scores that are higher than they would if a male database were used; in fact, many men will fracture at T-scores that are "normal." This highlights the importance of diagnosing osteoporosis not just by T-score, but also by the presence of fragility fracture and/or by estimations of fracture risk as generated by tools such as the FRAX calculator. The practical consequences of this change in densitometric definition of osteoporosis in men should be monitored, including the proportion of men at risk identified and treated as well as defining the response to treatment in those assessed by this more comprehensive approach. PMID:25255867

  20. Evidence-based recommendations on androgen deprivation therapy for localized and advanced prostate cancer

    PubMed Central

    Belsey, Jonathan; Drewa, Tomasz; Kołodziej, Anna; Skoneczna, Iwona; Milecki, Piotr; Dobruch, Jakub; Słojewski, Marcin; Chłosta, Piotr L.

    2016-01-01

    Introduction The management of prostate cancer (PC) is still evolving. Although, androgen deprivation therapy (ADT) is an established treatment option, particularly in patients with disseminated disease, important data regarding hormonal manipulation have recently emerged. The aim of this paper is to review the evidence on ADT, make recommendations and address areas of controversy associated with its use in men with PC. Material and methods An expert panel was convened. Areas related to the hormonal management of patients with PC requiring evidence review were identified and questions to be addressed by the panel were determined. Appropriate literature review was performed and included a search of online databases, bibliographic reviews and consultation with experts. Results The panel was able to provide recommendations on: 1) which patients with localised PC should receive androgen deprivation in conjunction with radiotherapy (RT); 2) what standard initial treatment should be used in metastatic hormone-naïve PC (MHNPC); 3) efficacy of androgen deprivation agents; 4) whether ADT should be continued in patients with castration resistant PC (CRPC). However, no recommendations could be made for combined ADT and very high-dose RT in patients with an intermediate-risk disease. Conclusions ADT remains the cornerstone of treatment for both metastatic hormone-naïve and castration-resistant PC. According to the expert panel's opinion, based on the ERG report, luteinizing hormone-releasing hormone agonists might not be equivalent but this needs to be confirmed in long-term data. The combined use of ADT and RT improves outcome and survival in men with high-risk localised disease. The benefits in patients with intermediate-risk disease, particularly those subject to escalated dose RT are controversial. PMID:27551549

  1. Androgen deprivation therapy and cardiovascular disease: what is the linking mechanism?

    PubMed Central

    Zareba, Piotr; Duivenvoorden, Wilhelmina; Leong, Darryl P.; Pinthus, Jehonathan H.

    2015-01-01

    The past decade has brought increased awareness of the potential adverse effects of androgen deprivation therapy (ADT) in men with prostate cancer. Arguably the most important and controversial of these is the increased risk of cardiovascular morbidity and mortality. Although multiple observational studies have shown that men treated with ADT are at increased risk of developing atherosclerotic cardiovascular disease, our understanding of the biological mechanisms that might underlie this phenomenon is still evolving. In this review, we discuss some of the mechanisms that have been proposed to date, including ADT-induced metabolic changes that promote the development and progression of atherosclerotic plaques as well as direct local effects of hormonal factors on plaque growth, rupture and thrombosis. PMID:27034724

  2. Androgen-deprivation therapy and bone loss in prostate cancer patients: a clinical review

    PubMed Central

    Bienz, Marc; Saad, Fred

    2015-01-01

    Androgen-deprivation therapy (ADT) has become a standard of care in the management of advanced prostate cancer or as an adjunct therapy. However, ADT is associated with a well-known deleterious effect on bone health, resulting in a decrease in bone-mass density (BMD) and increased risk for fracture. With the longer life expectancy of prostate cancer patients, improvement of the quality of life has become increasingly important. Therefore, adequate screening, prevention and treatment of BMD loss is paramount. Zoledronic acid and denosumab have shown promising results in recent studies, which has led to the Food and Drug Administration approval of these treatment options in various settings throughout the course of the disease, including the prevention of ADT-associated bone loss. This review focuses on the various parameters that impact BMD loss in men initiating ADT, on the specific effect of ADT on bone health and on various lifestyle modifications and treatment options such as bisphosphonates, osteoclast-targeted therapy and selective estrogen-receptor modulators that have shown promising results in recent studies. PMID:26131363

  3. Integrating diet and exercise into care of prostate cancer patients on androgen deprivation therapy

    PubMed Central

    Moyad, Mark A; Newton, Robert U; Tunn, Ulf W; Gruca, Damian

    2016-01-01

    Improved diagnosis and treatment regimens have resulted in greater longevity for men with prostate cancer. This has led to an increase in both androgen deprivation therapy (ADT) use and duration of exposure, and therefore to its associated adverse effects, such as sexual dysfunction, osteoporosis, reduced muscle mass, increased fat mass, and increased incidence of cardiovascular disease and type 2 diabetes. Given that the adverse effects of ADT are systemic, often debilitating, and difficult to treat, efforts continue in the development of new strategies for long-term management of prostate cancer. The PubMed database was searched to select trials, reviews, and meta-analyses in English using such search terms as “prostate cancer” and “androgen deprivation therapy”, “cardiovascular risk”, “lean body mass”, “exercise”, and “diet”. The initial searches produced 379 articles with dates 2005 or more recent. Articles published after 2004 were favored. This review utilizes the latest data to provide a status update on the effects of exercise and diet on patients with prostate cancer, focusing on ADT-associated side effects, and it discusses the evidence for such interventions. Since the evidence of large-scale trials in patients with prostate cancer is missing, and an extrapolation of supporting data to all patient subgroups cannot be provided, individualized risk assessments remain necessary before the initiation of exercise and diet programs. Exercise, diet, and nutritional supplementation interventions have the potential to provide effective, accessible, and relatively inexpensive strategies for mitigating ADT-associated toxicities without introducing additional adverse effects. PMID:27574584

  4. Androgen deprivation therapy, insulin resistance, and cardiovascular mortality: an inconvenient truth.

    PubMed

    Basaria, Shehzad

    2008-01-01

    Prostate cancer (PCa) is the most common cancer in men. Androgen deprivation therapy (ADT) is used in the treatment of locally advanced and metastatic PCa. Although its use as an adjuvant therapy has resulted in improved survival in some patients, ADT has negative consequences. Complications like osteoporosis, sexual dysfunction, gynecomastia, and adverse body composition are well known. Recent studies have also found metabolic complications in these men. Studies show that short-term ADT (3-6 months) results in development of hyperinsulinemia without causing hyperglycemia. Studies of men undergoing long-term (>or=12 months) ADT reveal higher prevalence of diabetes and metabolic syndrome compared with controls. In addition, men undergoing ADT also experience higher cardiovascular mortality. Long-term prospective studies of ADT are needed to determine the timing of onset of these complications and to employ strategies to prevent them. In the meantime, baseline and serial screening for fasting glucose and other cardiac risk factors in men receiving ADT is prudent. In selected cases, glucose tolerance testing and cardiac evaluation may be required. PMID:18567642

  5. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

    PubMed Central

    Mason, Malcolm D.; Parulekar, Wendy R.; Sydes, Matthew R.; Brundage, Michael; Kirkbride, Peter; Gospodarowicz, Mary; Cowan, Richard; Kostashuk, Edmund C.; Anderson, John; Swanson, Gregory; Parmar, Mahesh K.B.; Hayter, Charles; Jovic, Gordana; Hiltz, Andrea; Hetherington, John; Sathya, Jinka; Barber, James B.P.; McKenzie, Michael; El-Sharkawi, Salah; Souhami, Luis; Hardman, P.D. John; Chen, Bingshu E.; Warde, Padraig

    2015-01-01

    Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer. PMID:25691677

  6. Randomized, Double-Blinded, Placebo-Controlled, Trial of Risedronate for the Prevention of Bone Mineral Density Loss in Nonmetastatic Prostate Cancer Patients Receiving Radiation Therapy Plus Androgen Deprivation Therapy

    SciTech Connect

    Choo, Richard; Lukka, Himu; Cheung, Patrick; Corbett, Tom; Briones-Urbina, Rosario; Vieth, Reinhold; Ehrlich, Lisa; Kiss, Alex; Danjoux, Cyril

    2013-04-01

    Purpose: Androgen deprivation therapy (ADT) has been used as an adjuvant treatment to radiation therapy (RT) for the management of locally advanced prostate carcinoma. Long-term ADT decreases bone mineral density (BMD) and increases the risk of osteoporosis. The objective of this clinical trial was to evaluate the efficacy of risedronate for the prevention of BMD loss in nonmetastatic prostate cancer patients undergoing RT plus 2 to 3 years of ADT. Methods and Materials: A double-blinded, placebo-controlled, randomized trial was conducted for nonmetastatic prostate cancer patients receiving RT plus 2 to 3 years of ADT. All had T scores > −2.5 on dual energy x-ray absorptiometry at baseline. Patients were randomized 1:1 between risedronate and placebo for 2 years. The primary endpoints were the percent changes in the BMD of the lumbar spine at 1 and 2 years from baseline, measured by dual energy x-ray absorptiometry. Analyses of the changes in BMD and bone turnover biomarkers were carried out by comparing mean values of the intrapatient changes between the 2 arms, using standard t tests. Results: One hundred four patients were accrued between 2004 and 2007, with 52 in each arm. Mean age was 66.8 and 67.5 years for the placebo and risedronate, respectively. At 1 and 2 years, mean (±SE) BMD of the lumbar spine decreased by 5.77% ± 4.66% and 13.55% ± 6.33%, respectively, in the placebo, compared with 0.12% ± 1.29% at 1 year (P=.2485) and 0.85% ± 1.56% (P=.0583) at 2 years in the risedronate. The placebo had a significant increase in serum bone turnover biomarkers compared with the risedronate. Conclusions: Weekly oral risedronate prevented BMD loss at 2 years and resulted in significant suppression of bone turnover biomarkers for 24 months for patients receiving RT plus 2 to 3 years of ADT.

  7. Androgen deprivation therapy for prostate cancer is associated in increased risk for biliary disease

    PubMed Central

    Saylor, Philip J.; Smith, Matthew R.; O'Malley, A. James; Keating, Nancy L.

    2013-01-01

    Background Androgen deprivation therapy (ADT) for prostate cancer produces benefits in several clinical situations but has adverse metabolic effects including obesity, increased abdominal girth, increased triglycerides, and insulin resistance. Each of these is a risk factor for gallstone disease. ADT with a gonadotropin releasing hormone (GnRH) agonist was recently shown in metabolomic analyses to increase plasma levels of some bile acids. We assessed whether ADT is associated with an increased incidence of biliary disease. Methods We studied 249,977 men aged >65 living in Surveillance, Epidemiology, and End Results regions who were diagnosed with prostate cancer during 1992-2007 and followed through 2009. We calculated incidence rates for biliary disease during treatment with GnRH agonists, orchiectomy, or no therapy. We used Cox proportional hazard models to assess the association of ADT with biliary disease. Results Among 185,106 men with local/regional prostate cancer, 47.8% received GnRH agonist treatment and 2.2% underwent bilateral orchiectomy during follow-up. GnRH agonist treatment was associated with significantly higher incidence of biliary disease compared with no treatment (14.46 vs. 12.44 cases per 1,000 person years; P<0.001). In adjusted analyses GnRH agonist use was associated with risk of biliary disease (adjusted hazard ratio=1.09, 95% confidence interval 1.04–1.14; P <0.001). Orchiectomy was not significantly associated with biliary disease. Conclusions GnRH agonist treatment may be associated with an increased risk of incident biliary disease. This potential risk must be weighed against the potential benefits of therapy. PMID:23428068

  8. Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

    SciTech Connect

    Soto, Daniel E.; Passarelli, Michael N.; Daignault, Stephanie; Sandler, Howard M.

    2012-03-01

    Purpose: To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. Methods and Materials: A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjusted Cox proportional hazards modeling was performed to determine which factors predict PFS. Results: Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. Conclusions: This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.

  9. Biochemical Response to Androgen Deprivation Therapy Before External Beam Radiation Therapy Predicts Long-term Prostate Cancer Survival Outcomes

    SciTech Connect

    Zelefsky, Michael J.; Gomez, Daniel R.; Polkinghorn, William R.; Pei, Xin; Kollmeier, Marisa

    2013-07-01

    Purpose: To determine whether the response to neoadjuvant androgen deprivation therapy (ADT) defined by a decline in prostate-specific antigen (PSA) to nadir values is associated with improved survival outcomes after external beam radiation therapy (EBRT) for prostate cancer. Methods and Materials: One thousand forty-five patients with localized prostate cancer were treated with definitive EBRT in conjunction with neoadjuvant and concurrent ADT. A 6-month course of ADT was used (3 months during the neoadjuvant phase and 2 to 3 months concurrently with EBRT). The median EBRT prescription dose was 81 Gy using a conformal-based technique. The median follow-up time was 8.5 years. Results: The 10-year PSA relapse-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 74.3%, compared with 57.7% for patients with higher PSA nadir values (P<.001). The 10-year distant metastases-free survival outcome among patients with pre-radiation therapy PSA nadirs of ≤0.3 ng/mL was 86.1%, compared with 78.6% for patients with higher PSA nadir values (P=.004). In a competing-risk analysis, prostate cancer-related deaths were also significantly reduced among patients with pre-radiation therapy PSA nadirs of <0.3 ng/mL compared with higher values (7.8% compared with 13.7%; P=.009). Multivariable analysis demonstrated that the pre-EBRT PSA nadir value was a significant predictor of long-term biochemical tumor control, distant metastases-free survival, and cause-specific survival outcomes. Conclusions: Pre-radiation therapy nadir PSA values of ≤0.3 ng/mL after neoadjuvant ADT were associated with improved long-term biochemical tumor control, reduction in distant metastases, and prostate cancer-related death. Patients with higher nadir values may require alternative adjuvant therapies to improve outcomes.

  10. Opposing effects of androgen deprivation and targeted therapy on prostate cancer prevention

    PubMed Central

    Jia, Shidong; Gao, Xueliang; Lee, Sang Hyun; Maira, Sauveur-Michel; Wu, Xiaoqiu; Stack, Edward C.; Signoretti, Sabina; Loda, Massimo; Zhao, Jean J; Roberts, Thomas M.

    2012-01-01

    Prostate cancer is an ideal target for chemoprevention. To date, chemoprevention clinical trials with 5α-reductase inhibitors (5-ARI) have yielded encouraging yet ultimately confounding results. Using a pre-clinical mouse model of high-grade prostatic intraepithelial neoplasia (HG-PIN) induced by PTEN loss, we observed unprecedented deteriorating effects of androgen deprivation, where surgical castration or MDV3100 treatment accelerated disease progression of the otherwise stable HG-PIN to invasive castration-resistant prostate cancer (CRPC). As an alternative, targeting the PI3K signaling pathway via either genetic ablation of PI3K components or pharmacological inhibition of PI3K pathway reversed the PTEN loss-induced HG-PIN phenotype. Finally, concurrent inhibition of PI3K and MAPK pathways was effective in blocking the growth of PTEN-null CRPC. Together, these data have revealed the potential adverse effects of anti-androgen chemoprevention in certain genetic contexts (such as PTEN loss) while demonstrating the promise of targeted therapy in the clinical management of this complex and prevalent disease. PMID:23258246

  11. Effects of strength training on muscle cellular outcomes in prostate cancer patients on androgen deprivation therapy.

    PubMed

    Nilsen, T S; Thorsen, L; Fosså, S D; Wiig, M; Kirkegaard, C; Skovlund, E; Benestad, H B; Raastad, T

    2016-09-01

    Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross-sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 μm(2) , P = 0.04), with the only significant increase observed in type II fibers (1076 μm(2) , P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed. PMID:26282343

  12. The lived experience of physically active older prostate cancer survivors on androgen deprivation therapy.

    PubMed

    Wright-St Clair, Valerie A; Malcolm, Wanda; Keogh, Justin W L

    2014-03-01

    This study sought to explore the lived experiences of physically active prostate cancer survivors on androgen deprivation therapy (ADT), who exercise individually. Three older men (74-88 years old) with prostate cancer, using ADT continuously for at least 12 months and regularly exercising for at least 6 months, participated in this qualitative pilot study, informed by interpretive phenomenology. Data were gathered using individual semi-structured interviews, audio recorded and transcribed verbatim. Coherent stories were drawn from each transcript and analyzed using iterative and interpretive methods. van Manen's lifeworld existentials provided a framework for interpreting across the research text. Three notions emerged: Getting started, Having a routine and Being with music. Together they reveal what drew the participants to exercising regularly despite the challenges associated with their cancer and treatments. This study provides insights into the benefits of, and what it means for, older men with prostate cancer to regularly exercise individually. These findings may assist cancer clinicians and other allied health professionals to be more attuned to prostate cancer survivors' lived experiences when undergoing ADT, allowing clinicians to better promote regular exercise to their patients as a foundational component of living well. PMID:23862577

  13. The use of exercise interventions to overcome adverse effects of androgen deprivation therapy.

    PubMed

    Østergren, Peter Busch; Kistorp, Caroline; Bennedbæk, Finn Noe; Faber, Jens; Sønksen, Jens; Fode, Mikkel

    2016-06-01

    Androgen deprivation therapy (ADT) induces severe hypogonadism and is associated with several adverse effects that negatively affect health and quality of life in patients with prostate cancer. ADT changes body composition characterized by an increase in fat mass and a reduction in muscle mass and strength. Insulin sensitivity is also diminished and population-based studies indicate an increased risk of diabetes mellitus and cardiovascular disease in men receiving ADT. Particularly the first 6 months of treatment seem to hold an additional risk of new cardiovascular events for patients with already existing cardiovascular disease. In this initial phase of ADT, metabolic changes are also most prominent. In addition, ADT increases the rate of bone loss and fracture risk. Currently available evidence supports the use of exercise interventions to improve physical function and mitigate ADT-induced fatigue. Some studies also indicate that exercise might moderate ADT-related changes in body composition. However, beneficial effects of exercise interventions on other ADT-related conditions have not been conclusively proven. Trials investigating the effects of ADT on fracture risk and development of diabetes mellitus and cardiovascular disease are still warranted. Furthermore, studies investigating safety and effects of physical activity in men with bone metastases are lacking. PMID:27112391

  14. Psychological effects of androgen-deprivation therapy on men with prostate cancer and their partners.

    PubMed

    Donovan, Kristine A; Walker, Lauren M; Wassersug, Richard J; Thompson, Lora M A; Robinson, John W

    2015-12-15

    The clinical benefits of androgen-deprivation therapy (ADT) for men with prostate cancer (PC) have been well documented and include living free from the symptoms of metastases for longer periods and improved quality of life. However, ADT comes with a host of its own serious side effects. There is considerable evidence of the adverse cardiovascular, metabolic, and musculoskeletal effects of ADT. Far less has been written about the psychological effects of ADT. This review highlights several adverse psychological effects of ADT. The authors provide evidence for the effect of ADT on men's sexual function, their partner, and their sexual relationship. Evidence of increased emotional lability and depressed mood in men who receive ADT is also presented, and the risk of depression in the patient's partner is discussed. The evidence for adverse cognitive effects with ADT is still emerging but suggests that ADT is associated with impairment in multiple cognitive domains. Finally, the available literature is reviewed on interventions to mitigate the psychological effects of ADT. Across the array of adverse effects, physical exercise appears to have the greatest potential to address the psychological effects of ADT both in men who are receiving ADT and in their partners. PMID:26372364

  15. The Use of Dietary Supplements to Alleviate Androgen Deprivation Therapy Side Effects during Prostate Cancer Treatment

    PubMed Central

    Dueregger, Andrea; Heidegger, Isabel; Ofer, Philipp; Perktold, Bernhard; Ramoner, Reinhold; Klocker, Helmut; Eder, Iris E.

    2014-01-01

    Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT. PMID:25338271

  16. The use of dietary supplements to alleviate androgen deprivation therapy side effects during prostate cancer treatment.

    PubMed

    Dueregger, Andrea; Heidegger, Isabel; Ofer, Philipp; Perktold, Bernhard; Ramoner, Reinhold; Klocker, Helmut; Eder, Iris E

    2014-10-01

    Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT. PMID:25338271

  17. Androgen Deprivation Therapy and the Incidence of Inflammatory Bowel Disease in Patients With Prostate Cancer.

    PubMed

    Klil-Drori, Adi J; Tascilar, Koray; Yin, Hui; Aprikian, Armen; Bitton, Alain; Azoulay, Laurent

    2016-07-01

    Androgen deprivation therapy (ADT) is the mainstay treatment for advanced prostate cancer. By lowering androgen levels, ADT inhibits the progression of prostate cancer, but it may also affect gut autoimmunity. We investigated the association between ADT and the incidence of inflammatory bowel disease using a cohort of 31,842 men newly diagnosed with prostate cancer between 1988 and 2014, identified in the United Kingdom Clinical Practice Research Datalink. Exposure to ADT was treated as a time-varying variable and lagged by 1 year to account for diagnostic delays, with nonuse as the reference category. During 133,018 person-years of follow-up, 48 men were newly diagnosed with ulcerative colitis (incidence rate (IR) = 36/100,000 person-years (PY)) and 12 were diagnosed with Crohn's disease (IR = 9/100,000 PY). In Cox proportional hazards models, ADT was associated with a decreased risk of ulcerative colitis (IR = 24/100,000 PY vs. IR = 50/100,000 PY; hazard ratio = 0.52, 95% confidence interval: 0.28, 0.99) and a nonsignificant decreased risk of Crohn's disease (hazard ratio = 0.38, 95% confidence interval: 0.11, 1.37). These findings indicate that the use of ADT may be associated with intestinal autoimmunity. Further research is warranted to replicate these findings and assess their clinical significance. PMID:27268031

  18. Rising prostate-specific antigen values during neoadjuvant androgen deprivation therapy: The importance of monitoring

    SciTech Connect

    Niblock, Paddy; Pickles, Tom . E-mail: tpickles@bccancer.bc.ca

    2006-05-01

    Purpose: To assess the impact of a rising prostate-specific antigen (PSA) level in patients receiving neoadjuvant androgen deprivation therapy (N-ADT) before external beam radiotherapy for prostate cancer. Methods and Materials: From prospectively collected data, we identified 182 patients who received between 3 and 12 months of N-ADT before definitive external beam radiotherapy and who had at least three PSA readings during the neoadjuvant period. One hundred fifty patients had PSA values that continued to fall (Non-Rise group), but 32 had a PSA value that started to rise (Rise group). The two groups were compared by Mann-Whitney U and Pearson chi-square tests. Kaplan-Meier and log-rank analyses were performed for time to treatment failure, cause-specific survival (CSS), and overall survival (OS). Results: The median follow-up was 62.5 months for the Non-Rise group and 53 months for the Rise group. Patients who sustained a PSA rise during the N-ADT period had a shorter time to PSA relapse (p = 0.013), poorer CSS (p = 0.027), and poorer OS (p = 0.03). Multivariate analysis confirms the significance of a PSA rise during the N-ADT period for CSS (p = 0.035) and OS (p = 0.038). Conclusions:: A subset of patients treated with N-ADT develop a rising PSA profile that likely represents early androgen resistance. They have significantly worse outcome.

  19. Impact of Concurrent Androgen Deprivation on Fiducial Marker Migration in External-beam Radiation Therapy for Prostate Cancer

    SciTech Connect

    Tiberi, David A.; Carrier, Jean-Francois; Beauchemin, Marie-Claude; Nguyen, Thu Van; Beliveau-Nadeau, Dominic; Taussky, Daniel

    2012-09-01

    Purpose: To determine the extent of gold fiducial marker (FM) migration in patients treated for prostate cancer with concurrent androgen deprivation and external-beam radiation therapy (EBRT). Methods and Materials: Three or 4 gold FMs were implanted in 37 patients with prostate adenocarcinoma receiving androgen deprivation therapy (ADT) in conjunction with 70-78 Gy. Androgen deprivation therapy was started a median of 3.9 months before EBRT (range, 0.3-12.5 months). To establish the extent of FM migration, the distance between each FM was calculated for 5-8 treatments once per week throughout the EBRT course. For each treatment, the distance between FMs was compared with the distance from the digitally reconstructed radiographs generated from the planning CT. A total of 281 treatments were analyzed. Results: The average daily migration was 0.8 {+-} 0.3 mm, with distances ranging from 0.2 mm-2.6 mm. Two of the 281 assessed treatments (0.7%) showed migrations >2 mm. No correlation between FM migration and patient weight or time delay between ADT and start of EBRT was found. There was no correlation between the extent of FM migration and prostate volume. Conclusion: This is the largest report of implanted FM migration in patients receiving concomitant ADT. Only 0.7% of the 281 treatments studied had significant marker migrations (>2 mm) throughout the course of EBRT. Consequently, the use of implanted FMs in these patients enables accurate monitoring of prostate gland position during treatment.

  20. Bone Scan Index as a prognostic imaging biomarker during androgen deprivation therapy

    PubMed Central

    2014-01-01

    Background Bone Scan Index (BSI) is a quantitative measurement of tumour burden in the skeleton calculated from bone scan images. When analysed at the time of diagnosis, it has been shown to provide prognostic information on survival in men with metastatic prostate cancer (PCa). In this study, we evaluated the prognostic value of BSI during androgen deprivation therapy (ADT). Methods Prostate cancer patients who were at high risk of a poor outcome and who had undergone bone scan at the time of diagnosis and during ADT were recruited from two university hospitals for a retrospective study. BSI at baseline and follow-up were calculated using an automated software package (EXINIbonebsi). Associations between BSI, other prognostic biomarkers and overall survival (OS) were evaluated using a Cox proportional hazards regression model. Results One hundred forty-six PCa patients were included in the study. A total of 102 patient deaths were registered, with a median survival time after the follow-up bone scan of 2.4 years (interquartile range (IQR) =0.8 to 4.4). Both at baseline and during ADT, BSI was significantly associated with OS in univariate and multivariate analyses. When BSI was added to a prognostic base model including age, prostate-specific antigen, clinical tumour stage and Gleason score, the concordance index increased from 0.73 to 0.77 (p =0.0005) at baseline and from 0.77 to 0.82 (p <0.0001) during ADT. Conclusions Automated BSI during ADT is an independent prognostic indicator of OS in PCa patients with bone metastasis. It represents an emerging imaging biomarker that can be used in a prognostic model for risk stratification of PCa patients at the time of diagnosis and at later stages of the disease. BSI could then help physicians identify patients who could benefit from more aggressive therapies. PMID:25386390

  1. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men With Locally Advanced Prostate Cancer

    PubMed Central

    Bekelman, Justin E.; Mitra, Nandita; Handorf, Elizabeth A.; Uzzo, Robert G.; Hahn, Stephen A.; Polsky, Daniel; Armstrong, Katrina

    2015-01-01

    Purpose We examined whether the survival advantage of androgen-deprivation therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with locally advanced prostate cancer reported in two randomized trials holds in real-world clinical practice and extended the evidence to patients poorly represented in the trials. Methods We conducted nonrandomized effectiveness studies of ADT plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007 and observed through 2009 in the SEER-Medicare data set: (1) the randomized clinical trial (RCT) cohort, which included men age 65 to 75 years and was most consistent with participants in the randomized trials; (2) the elderly cohort, which included men age > 75 years with locally advanced prostate cancer; and (3) the screen-detected cohort, which included men age ≥ 65 years with screen-detected high-risk prostate cancer. We evaluated cause-specific and all-cause mortality using propensity score, instrumental variable (IV), and sensitivity analyses. Results In the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality relative to ADT alone (cause-specific propensity score–adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all-cause propensity score–adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness estimates for the RCT cohort were not significantly different from those from randomized trials (P > .1). In the elderly and screen-detected cohorts, ADT plus RT was also associated with reduced cause-specific and all-cause mortality. IV analyses produced estimates similar to those from propensity score–adjusted methods. Conclusion Older men with locally advanced or screen-detected high-risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival. PMID:25559808

  2. Football training improves lean body mass in men with prostate cancer undergoing androgen deprivation therapy.

    PubMed

    Uth, J; Hornstrup, T; Schmidt, J F; Christensen, J F; Frandsen, C; Christensen, K B; Helge, E W; Brasso, K; Rørth, M; Midtgaard, J; Krustrup, P

    2014-08-01

    Androgen deprivation therapy (ADT) remains a cornerstone in the management of patients with prostate cancer (PCa) despite adverse effects on body composition and functional parameters. We compared the effects of football training with standard care in PCa patients managed with ADT (> 6 months). Fifty-seven men aged 67 (range: 43-74) were randomly assigned to a football group (FG, n = 29) or a usual care control group (CON, n = 28). The primary outcome was change in lean body mass (LBM) assessed by dual-energy X-ray absorptiometry scanning. Secondary outcomes included changes in knee-extensor muscle strength (one repetition maximum), fat percentage, and maximal oxygen uptake (VO2max ). Mean heart rate during training was 137.7 (standard deviation 13.7) bpm or 84.6 (3.9)% HRmax. In FG, LBM increased by 0.5 kg [95% confidence interval (CI) 0.1-0.9; P = 0.02] with no change in CON (mean group difference 0.7 kg; 95% CI 0.1-1.2; P = 0.02). Also, muscle strength increased in FG (8.9 kg; 95% CI 6.0-11.8; P < 0.001) with no change in CON (mean group difference 6.7 kg; 95% CI 2.8-10.7; P < 0.001). In FG, VO2max increased (1.0 mL/kg/min; 95% CI 0.2-1.9; P = 0.02) and fat percentage tended to decrease (0.7%; 95%CI 1.3-0.0; P = 0.06), but these changes were not significantly different from CON. In conclusion, football training over 12 weeks improved LBM and muscle strength compared with usual care in men with prostate cancer receiving ADT. PMID:24944134

  3. Health care costs for prostate cancer patients receiving androgen deprivation therapy: treatment and adverse events

    PubMed Central

    Krahn, M.D.; Bremner, K.E.; Luo, J.; Alibhai, S.M.H.

    2014-01-01

    Background Serious adverse events have been associated with androgen deprivation therapy (adt) for prostate cancer (pca), but few studies address the costs of those events. Methods All pca patients (ICD-9-CM 185) in Ontario who started 90 days or more of adt or had orchiectomy at the age of 66 or older during 1995–2005 (n = 26,809) were identified using the Ontario Cancer Registry and drug and hospital data. Diagnosis dates of adverse events—myocardial infarction, acute coronary syndrome, congestive heart failure, stroke, deep vein thrombosis or pulmonary embolism, any diabetes, and fracture or osteoporosis—before and after adt initiation were determined from administrative data. We excluded patients with the same diagnosis before and after adt, and we allocated each patient’s time from adt initiation to death or December 31, 2007, into health states: adt (no adverse event), adt-ae (specified single adverse event), Multiple (>1 event), and Final (≤180 days before death). We used methods for Canadian health administrative data to estimate annual total health care costs during each state, and we examined monthly trends. Results Approximately 50% of 21,811 patients with no pre-adt adverse event developed 1 or more events after adt. The costliest adverse event state was stroke ($26,432/year). Multiple was the most frequent (n = 2,336) and the second most costly health state ($24,374/year). Costs were highest in the first month after diagnosis (from $1,714 for diabetes to $14,068 for myocardial infarction). Costs declined within 18 months, ranging from $784 per 30 days (diabetes) to $1,852 per 30 days (stroke). Adverse events increased the costs of adt by 100% to 265%. Conclusions The economic burden of adverse events is relevant to programs and policies from clinic to government, and that burden merits consideration in the risks and benefits of adt. PMID:24940106

  4. Depressive Symptomatology in Men Receiving Androgen Deprivation Therapy for Prostate Cancer: A Controlled Comparison

    PubMed Central

    Lee, Morgan; Jim, Heather S.; Fishman, Mayer; Zachariah, Babu; Heysek, Randy; Biagioli, Matthew; Jacobsen, Paul B.

    2014-01-01

    Objective Prostate cancer patients who receive androgen deprivation therapy (ADT) often experience many physical and psychological side effects. ADT may be associated with increased risk for depression, but the relationship between ADT and depression is not fully understood. This study used a longitudinal design to assess depressive symptomatology in patients receiving ADT compared to two groups of matched controls. Methods Participants were men initiating ADT treatment (ADT+ group; n = 61) and their matched controls: prostate cancer patients treated with radical prostatectomy (ADT− group; n = 61) and no-cancer controls (CA− group; n = 61). Depressive symptomatology was assessed using the Center for Epidemiological Studies Depression Scale at ADT initiation and again six months later. Differences in depressive symptomatology and rates of clinically-significant depressive symptomatology were analyzed between groups at each time point and within groups over time. Results: Between baseline and follow-up, ADT+ participants demonstrated increased depressive symptomatology and increased rates of clinically-significant depressive symptomatology (ps < .05). ADT+ participants also reported greater depressive symptomatology than both control groups at follow-up (ps < .001). Rates of clinically-significant depressive symptomatology were higher in the ADT+ group than the ADT− and CA− groups at both time points (baseline: 28%, 5%, 12%; follow-up: 39%, 9%, 11%). Conclusions Findings support the hypothesis that ADT administration yields increases in depression and suggest that the mechanism behind ADT’s association with depression should be explored and that prostate cancer patients treated with ADT should receive particular focus in depression screening and intervention. PMID:24924331

  5. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial

    PubMed Central

    Warde, Padraig; Mason, Malcolm; Ding, Keyue; Kirkbride, Peter; Brundage, Michael; Cowan, Richard; Gospodarowicz, Mary; Sanders, Karen; Kostashuk, Edmund; Swanson, Greg; Barber, Jim; Hiltz, Andrea; Parmar, Mahesh KB; Sathya, Jinka; Anderson, John; Hayter, Charles; Hetherington, John; Sydes, Matthew R; Parulekar, Wendy

    2011-01-01

    Summary Background Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Methods Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65–69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Results Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4–8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70–78 vs 66%, 60–70; hazard ratio [HR] 0·77, 95% CI 0·61–0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). Interpretation The benefits of combined

  6. High-Dose Adjuvant Radiotherapy After Radical Prostatectomy With or Without Androgen Deprivation Therapy

    SciTech Connect

    Ost, Piet; Cozzarini, Cesare; De Meerleer, Gert; Fiorino, Claudio; De Potter, Bruno; Briganti, Alberto; Nagler, Evi V.T.; Montorsi, Francesco; Fonteyne, Valerie; Di Muzio, Nadia

    2012-07-01

    Purpose: To retrospectively evaluate the outcome and toxicity in patients receiving high-dose (>69 Gy) adjuvant radiotherapy (HD-ART) and the impact of androgen deprivation therapy (ADT). Methods and Materials: Between 1999 and 2008, 225 node-negative patients were referred for HD-ART with or without ADT to two large academic institutions. Indications for HD-ART were extracapsular extension, seminal vesicle invasion (SVI), and/or positive surgical margins at radical prostatectomy (RP). A dose of at least 69.1 Gy was prescribed to the prostate bed and seminal vesicle bed. The ADT consisted of a luteinizing hormone-releasing hormone analog. The duration and indication of ADT was left at the discretion of the treating physician. The effect of HD-ART and ADT on biochemical (bRFS) and clinical (cRFS) relapse-free survival was examined through univariate and multivariate analysis, with correction for known patient- and treatment-related variables. Interaction terms were introduced to evaluate effect modification. Results: After a median follow-up time of 5 years, the 7-year bRFS and cRFS were 84% and 88%, respectively. On multivariate analysis, the addition of ADT was independently associated with an improved bRFS (hazard ratio [HR] 0.4, p = 0.02) and cRFS (HR 0.2, p = 0.008). Higher Gleason scores and SVI were associated with decreased bRFS and cRFS. A lymphadenectomy at the time of RP independently improved cRFS (HR 0.09, p = 0.009). The 7-year probability of late Grade 2-3 toxicity was 29% and 5% for genitourinary (GU) and gastrointestinal (GI) symptoms, respectively. The absolute incidence of Grade 3 toxicity was <1% and 10% for GI and GU symptoms, respectively. The study is limited by its retrospective design and the lack of a standardized use of ADT. Conclusions: This retrospective study shows significantly improved bRFS and cRFS rates with the addition of ADT to HD-ART, with low Grade 3 gastrointestinal toxicity and 10% Grade 3 genitourinary toxicity.

  7. Substrate deprivation therapy: a new hope for patients suffering from neuronopathic forms of inherited lysosomal storage diseases.

    PubMed

    Jakóbkiewicz-Banecka, Joanna; Wegrzyn, Alicja; Wegrzyn, Grzegorz

    2007-01-01

    Lysosomal storage diseases are a group of disorders caused by defects in enzymes responsible for degradation of particular compounds in lysosomes. In most cases, these diseases are fatal, and until recently no treatment was available. Introduction of enzyme replacement therapy was a breakthrough in the treatment of some of the diseases. However, while this therapy is effective in reduction of many somatic symptoms, its efficacy in the treatment of the central nervous system is negligible, if any, mainly because of problems with crossing the blood-brain-barrier by intravenously administered enzyme molecules. On the other hand, there are many lysosomal storage diseases in which the central nervous system is affected. Results of very recent studies indicate that in at least some cases, another type of therapy, called substrate deprivation therapy (or substrate reduction therapy) may be effective in the treatment of neuronopathic forms of lysosomal storage diseases. This therapy, based on inhibition of synthesis of the compounds that cannot be degraded in cells of the patients, has been shown to be effective in several animal models of various diseases, and recent reports demonstrate its efficacy in the treatment of patients suffering from Niemann-Pick C disease and Sanfilippo disease. PMID:17998597

  8. Exercise improves quality of life in androgen deprivation therapy-treated prostate cancer: systematic review of randomised controlled trials.

    PubMed

    Teleni, Laisa; Chan, Raymond J; Chan, Alexandre; Isenring, Elisabeth A; Vela, Ian; Inder, Warrick J; McCarthy, Alexandra L

    2016-02-01

    Men receiving androgen deprivation therapy (ADT) for prostate cancer (PCa) are likely to develop metabolic conditions such as diabetes, cardiovascular disease, abdominal obesity and osteoporosis. Other treatment-related side effects adversely influence quality of life (QoL) including vasomotor distress, depression, anxiety, mood swings, poor sleep quality and compromised sexual function. The objective of this study was to systematically review the nature and effects of dietary and exercise interventions on QoL, androgen deprivation symptoms and metabolic risk factors in men with PCa undergoing ADT. An electronic search of CINAHL, CENTRAL, Medline, PsychINFO and reference lists was performed to identify peer-reviewed articles published between January 2004 and December 2014 in English. Eligible study designs included randomised controlled trials (RCTs) with pre- and post-intervention data. Data extraction and assessment of methodological quality with the Cochrane approach was conducted by two independent reviewers. Seven exercise studies were identified. Exercise significantly improved QoL, but showed no effect on metabolic risk factors (weight, waist circumference, lean or fat mass, blood pressure and lipid profile). Two dietary studies were identified, both of which tested soy supplements. Soy supplementation did not improve any outcomes. No dietary counselling studies were identified. No studies evaluated androgen-deficiency symptoms (libido, erectile function, sleep quality, mood swings, depression, anxiety and bone mineral density). Evidence from RCTs indicates that exercise enhances health- and disease-specific QoL in men with PCa undergoing ADT. Further studies are required to evaluate the effect of exercise and dietary interventions on QoL, androgen deprivation symptoms and metabolic risk factors in this cohort. PMID:26584972

  9. Hypoxia-Independent Downregulation of Hypoxia-Inducible Factor 1 Targets by Androgen Deprivation Therapy in Prostate Cancer

    SciTech Connect

    Ragnum, Harald Bull; Røe, Kathrine; Holm, Ruth; Vlatkovic, Ljiljana; Nesland, Jahn Marthin; Aarnes, Eva-Katrine; Ree, Anne Hansen; Flatmark, Kjersti; Seierstad, Therese; Lilleby, Wolfgang; Lyng, Heidi

    2013-11-15

    Purpose: We explored changes in hypoxia-inducible factor 1 (HIF1) signaling during androgen deprivation therapy (ADT) of androgen-sensitive prostate cancer xenografts under conditions in which no significant change in immunostaining of the hypoxia marker pimonidazole had occurred. Methods and Materials: Gene expression profiles of volume-matched androgen-exposed and androgen-deprived CWR22 xenografts, with similar pimonidazole-positive fractions, were compared. Direct targets of androgen receptor (AR) and HIF1 transcription factors were identified among the differentially expressed genes by using published lists. Biological processes affected by ADT were determined by gene ontology analysis. HIF1α protein expression in xenografts and biopsy samples from 35 patients receiving neoadjuvant ADT was assessed by immunohistochemistry. Results: A total of 1344 genes showed more than 2-fold change in expression by ADT, including 35 downregulated and 5 upregulated HIF1 targets. Six genes were shared HIF1 and AR targets, and their downregulation was confirmed with quantitative RT-PCR. Significant suppression of the biological processes proliferation, metabolism, and stress response in androgen-deprived xenografts was found, consistent with tumor regression. Nineteen downregulated HIF1 targets were involved in those significant biological processes, most of them in metabolism. Four of these were shared AR and HIF1 targets, including genes encoding the regulatory glycolytic proteins HK2, PFKFB3, and SLC2A1. Most of the downregulated HIF1 targets were induced by hypoxia in androgen-responsive prostate cancer cell lines, confirming their role as hypoxia-responsive HIF1 targets in prostate cancer. Downregulation of HIF1 targets was consistent with the absence of HIF1α protein in xenografts and downregulation in patients by ADT (P<.001). Conclusions: AR repression by ADT may lead to downregulation of HIF1 signaling independently of hypoxic fraction, and this may contribute to

  10. Low-Energy Fractures without Low T-Scores Characteristic of Osteoporosis

    PubMed Central

    Malluche, Hartmut H.; Porter, Daniel S.; Mawad, Hanna; Monier-Faugere, Marie-Claude; Pienkowski, David

    2013-01-01

    Background: Osteoporotic fractures commonly occur after low-energy trauma in postmenopausal women with reduced bone quantity documented by low bone mineral density (BMD). Low-energy fractures, however, have also been reported to occur in premenopausal women with normal or near-normal BMD, suggesting the existence of a bone quality abnormality. Methods: Bone quality and quantity were evaluated in a cross-sectional study of three groups of premenopausal white females: (1) twenty-five subjects with low-energy fracture(s) and BMD in the normal range (t-scores > −2.0), (2) eighteen subjects with low-energy fracture(s) and BMD in the osteoporotic range (t-scores ≤ −2.5), and (3) fourteen healthy volunteers (controls). Bone quality was assessed with use of Fourier transform infrared spectroscopy and histomorphometry in iliac crest bone samples obtained from all subjects; bone quantity was assessed by dual x-ray absorptiometry and histomorphometry. Results: The collagen crosslinking ratio in the non-low-BMD subjects with fractures was 13% greater than the ratio in the low-BMD subjects with fractures and 14% greater than the ratio in the controls (p < 0.001 for both). Cancellous bone volume was 29% greater (p < 0.01) and trabecular separation was 31% less (p < 0.01) in the non-low-BMD subjects with fractures than in the low-BMD subjects with fractures; the values in the non-low-BMD subjects did not differ from those in the controls. Bone turnover did not differ among the groups, and osteomalacia was not present in any subject. Thus, the non-low-BMD subjects with fractures maintained bone quantity, but the collagen crosslinking ratio, a parameter of bone quality, was abnormal. In contrast, the low-BMD subjects with fractures did not have this collagen crosslinking abnormality but did have abnormal bone quantity. Conclusions: This study highlights a collagen crosslinking abnormality in patients with low-energy fractures and nonosteoporotic t-scores. Reports have

  11. Androgen-deprivation therapy does not impact cause-specific or overall survival after permanent prostate brachytherapy

    SciTech Connect

    Merrick, Gregory S. . E-mail: gmerrick@wheelinghospital.com; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A. M.S.; Adamovich, Edward

    2006-07-01

    Purpose: To determine if androgen-deprivation therapy (ADT) has an impact on cause-specific, biochemical progression-free, or overall survival after prostate brachytherapy. Methods and Materials: From April 1995 through June 2002, 938 consecutive patients underwent brachytherapy for clinical Stage T1b to T3a (2002 AJCC) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. A total of 382 patients (40.7%) received ADT with a duration of 6 months or less in 277 and more than 6 months in 105. The median follow-up was 5.4 years. Multiple clinical, treatment, and dosimetric parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. Results: The 10-year cause-specific, biochemical progression-free, and overall survival rates for the entire cohort were 96.4%, 95.9%, and 78.1%, respectively. Except for biochemical progression-free survival in high-risk patients, ADT did not statistically impact any of the three survival categories. A Cox linear-regression analysis demonstrated that Gleason score was the best predictor of cause-specific survival, whereas percent-positive biopsies, prostate volume, and risk group predicted for biochemical progression-free survival. Patient age and tobacco use were the strongest predictors of overall survival. One hundred two patients have died, with 80 of the deaths a result of cardiovascular disease (54) and second malignancies (26). To date, only 12 patients have died of metastatic prostate cancer. Conclusions: After brachytherapy, androgen-deprivation therapy did not have an impact on cause-specific or overall survival for any risk group; however, ADT had a beneficial effect on biochemical progression-free survival in high-risk patients. Cardiovascular disease and second malignancies far outweighed prostate cancer as competing causes of death.

  12. Androgen deprivation therapy did not increase the risk of Alzheimer's and Parkinson's disease in patients with prostate cancer.

    PubMed

    Chung, S D; Lin, H C; Tsai, M C; Kao, L T; Huang, C Y; Chen, K C

    2016-05-01

    Androgen deprivation therapy (ADT) has been the standard treatment for advanced prostate cancer for many decades. Although potential adverse effects of ADT have been reported, there are no empirical studies investigating the association between ADT and Alzheimer's disease. Therefore, this retrospective cohort study explored the relationship between the use of ADT and the subsequent risk of Alzheimer's disease in men with prostate cancer using a population-based database. We retrieved data from the "Taiwan Longitudinal Health Insurance Database 2000." The study included 1335 patients with prostate cancer and 4005 age-matched comparison patients without prostate malignancy. We then individually tracked each patient (n = 5340) for a 5-year period to discriminate those who subsequently received a diagnosis of Alzheimer's disease. The Cox proportional hazard regression showed that the hazard ratio (HR) for Alzheimer's disease during the 5-year follow-up period for prostate cancer patients was 1.71 (95% confidence interval (CI) = 0.90~3.25) over that of comparison patients. We further analyzed the hazard ratio for Alzheimer's disease and Parkinson's disease between prostate cancer patients who did and those who did not receive ADT, but we failed to observe a significant difference in the hazard ratio for both diseases during the 5-year follow-up period (adjusted HR = 1.76, 95% CI = 0.55~5.62, and HR = 1.13, 95% CI = 0.58~2.20, respectively). In conclusion, this study demonstrated that the use of androgen deprivation therapy in patients with prostate cancer was not associated with a higher risk of Alzheimer's and Parkinson's disease during the follow-up period. PMID:27062333

  13. Does androgen-deprivation therapy accelerate the development of frailty in older men with prostate cancer?: a conceptual review.

    PubMed

    Bylow, Kathryn; Mohile, Supriya G; Stadler, Walter M; Dale, William

    2007-12-15

    The majority of men with prostate cancer are aged > or =65 years. Men, as they age, are more likely to suffer from impaired physical function. The standard treatment for recurrent prostate cancer is androgen-deprivation therapy (ADT). Well-established toxicities from ADT include lean weight loss or sarcopenia, muscle weakness, fatigue, and reduced activity levels. Frailty is a term from geriatrics that describes older individuals with limited physiologic reserve who are at significant risk for adverse outcomes, including falls, disability, hospitalization, and death. An increasingly accepted definition of frailty is a syndrome in which > or =3 of the following are present: unintentional (lean) weight loss > or =10 pounds in the past year, weakness (measured by grip strength), slow walking speed, self-reported exhaustion, and low physical activity. This clinical syndrome overlaps closely with the known toxicities of ADT. In addition, alterations in the inflammatory system, neuroendocrine system, and energy production are associated with this syndrome, as evidenced by biomarkers such as C-reactive protein, interleukin-6, and tumor necrosis factor-alpha. For this article, the authors reviewed the evidence for the effect of ADT on each of the 5 frailty components plus the identified biomarkers, and the evidence indicates that ADT may accelerate the development of frailty in vulnerable older men with prostate cancer. Given the association of frailty with important clinical outcomes such as hospitalization and death, this potential consequence of ADT should be considered carefully when initiating therapy in older patients with recurrent prostate cancer. PMID:17960609

  14. Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy

    PubMed Central

    Storer, Thomas W; Miciek, Renee; Travison, Thomas G

    2012-01-01

    Prostate cancer (PCa) is the most common visceral malignancy in men with androgen deprivation therapy (ADT) the preferred therapy to suppress testosterone production and hence tumor growth. Despite its effectiveness in lowering testosterone, ADT is associated with side effects including loss of muscle mass, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life. This review reports a survey of the literature with a focus on changes in muscle strength, physical function and body composition, due to short-term and long-term ADT. Studies in these areas are sparse, especially well-controlled, prospective randomized trials. Cross-sectional and longitudinal data (up to 2 years) for men with PCa treated with ADT as well as patients with PCa not receiving ADT and age-matched healthy men are presented when available. Based on limited longitudinal data, the adverse effects of ADT on muscle function, physical performance and body composition occur shortly after the onset of ADT and tend to persist and worsen over time. Exercise training is a safe and effective intervention for mitigating these changes and initial guidelines for exercise program design for men with PCa have been published by the American College of Sports Medicine. Disparities in study duration, types of studies and other patient-specific variables such as time since diagnosis, cancer stage and comorbidities may all affect an understanding of the influence of ADT on health, physical performance and mortality. PMID:22367184

  15. Development of a spirometry T-score in the general population

    PubMed Central

    Lee, Sei Won; Kim, Hyun Kuk; Baek, Seunghee; Jung, Ji-Ye; Kim, Young Sam; Lee, Jae Seung; Lee, Sang-Do; Mannino, David M; Oh, Yeon-Mok

    2016-01-01

    Background and objective Spirometry values may be expressed as T-scores in standard deviation units relative to a reference in a young, normal population as an analogy to the T-score for bone mineral density. This study was performed to develop the spirometry T-score. Methods T-scores were calculated from lambda-mu-sigma-derived Z-scores using a young, normal age reference. Three outcomes of all-cause death, respiratory death, and COPD death were evaluated in 9,101 US subjects followed for 10 years; an outcome of COPD-related health care utilization (COPD utilization) was evaluated in 1,894 Korean subjects followed for 4 years. Results The probability of all-cause death appeared to remain nearly zero until −1 of forced expiratory volume in 1 second (FEV1) T-score but increased steeply where FEV1 T-score reached below −2.5. Survival curves for all-cause death, respiratory death, COPD death, and COPD utilization differed significantly among the groups when stratified by FEV1 T-score (P<0.001). The adjusted hazard ratios of the FEV1 T-score for the four outcomes were 0.54 (95% confidence interval, 0.48–0.60), 0.43 (95% CI: 0.37–0.50), 0.30 (95% CI: 0.24–0.37), and 0.69 (95% CI: 0.59–0.81), respectively, adjusting for covariates (P<0.001). Conclusion The spirometry T-score could predict all-cause death, respiratory death, COPD death, and COPD utilization. PMID:26966359

  16. Improvement in behaviour after substrate deprivation therapy with rhodamine B in a mouse model of MPS IIIA.

    PubMed

    Roberts, Ainslie L K; Rees, Matthew H; Klebe, Sonja; Fletcher, Janice M; Byers, Sharon

    2007-01-01

    Mucopolysaccharidosis type IIIA (MPS IIIA) is a specific lysosomal storage disorder caused by an enzyme deficiency in sulphamidase, which is required for the degradation of heparan sulphate glycosaminoglycan (gag). This deficiency results in widespread gag storage and leads to severe CNS degeneration and mild somatic pathology. We have developed substrate deprivation as a therapy (SDT) for MPS disorders to reduce the initial production of gag substrate for the deficient enzyme, using the compound rhodamine B as an inhibitor of gag biosynthesis. This should restore the balance between gag level and residual enzyme activity towards normal and improve patient outcome. To determine if SDT improved CNS function, MPS IIIA mice were treated for 6months with weekly, intravenous 1mg/kg rhodamine B and then tested in a 4-arm water cross maze, which measures spatial learning and memory. MPS IIIA untreated mice were unable to perform to the same level as normal littermates, having increased escape latency, increased incorrect entries and decreased correct entries. Rhodamine B treatment improved MPS IIIA performance towards normal with treated mice having decreased escape latency, decreased incorrect entries and increased correct entries when compared to MPS IIIA untreated littermates. This provides the first report of SDT resulting in a beneficial effect on CNS function in an MPS disorder and SDT targeting gag synthesis may be a viable treatment option for children with MPS. PMID:17681480

  17. Androgen Receptor Roles in Insulin Resistance and Obesity in Males: The Linkage of Androgen-Deprivation Therapy to Metabolic Syndrome

    PubMed Central

    Yu, I-Chen; Lin, Hung-Yun; Sparks, Janet D.; Yeh, Shuyuan

    2014-01-01

    Prostate cancer (PCa) is one of the most frequently diagnosed malignancies in men. Androgen-deprivation therapy (ADT) is the first-line treatment and fundamental management for men with advanced PCa to suppress functions of androgen/androgen receptor (AR) signaling. ADT is effective at improving cancer symptoms and prolonging survival. However, epidemiological and clinical studies support the notion that testosterone deficiency in men leads to the development of metabolic syndrome that increases cardiovascular disease risk. The underlying mechanisms by which androgen/AR signaling regulates metabolic homeostasis in men are complex, and in this review, we discuss molecular mechanisms mediated by AR signaling that link ADT to metabolic syndrome. Results derived from various AR knockout mouse models reveal tissue-specific AR signaling that is involved in regulation of metabolism. These data suggest that steps be taken early to manage metabolic complications associated with PCa patients receiving ADT, which could be accomplished using tissue-selective modulation of AR signaling and by treatment with insulin-sensitizing agents. PMID:25249645

  18. Sunitinib Plus Androgen Deprivation and Radiation Therapy for Patients With Localized High-Risk Prostate Cancer: Results From a Multi-institutional Phase 1 Study

    SciTech Connect

    Corn, Paul G.; Song, Danny Y.; Heath, Elisabeth; Maier, Jordan; Meyn, Raymond; Kuban, Deborah; DePetrillo, Thomas A.; Mathew, Paul

    2013-07-01

    Purpose: To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer. Methods and Materials: Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib. Results: Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy. Conclusions: The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

  19. Strength Training Induces Muscle Hypertrophy and Functional Gains in Black Prostate Cancer Patients Despite Androgen Deprivation Therapy

    PubMed Central

    Hurley, Ben F.

    2013-01-01

    Background. Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with weakness, fatigue, sarcopenia, and reduced quality of life (QoL). Black men have a higher incidence and mortality from PCa than Caucasians. We hypothesized that despite ADT, strength training (ST) would increase muscle power and size, thereby improving body composition, physical function, fatigue levels, and QoL in older black men with PCa. Methods. Muscle mass, power, strength, endurance, physical function, fatigue perception, and QoL were measured in 17 black men with PCa on ADT before and after 12 weeks of ST. Within-group differences were determined using t tests and regression models. Results. ST significantly increased total body muscle mass (2.7%), thigh muscle volume (6.4%), power (17%), and strength (28%). There were significant increases in functional performance (20%), muscle endurance (110%), and QoL scores (7%) and decreases in fatigue perception (38%). Improved muscle function was associated with higher functional performance (R 2 = 0.54) and lower fatigue perception (R 2 = 0.37), and both were associated with improved QoL (R 2 = 0.45), whereas fatigue perception tended to be associated with muscle endurance (R 2 = 0.37). Conclusions. ST elicits muscle hypertrophy even in the absence of testosterone and is effective in counteracting the adverse functional consequences of ADT in older black men with PCa. These improvements are associated with reduced fatigue perception, enhanced physical performance, and improved QoL. Thus, ST may be a safe and well-tolerated therapy to prevent the loss of muscle mass, strength, and power commonly observed during ADT. PMID:23089339

  20. Predictors of Androgen Deprivation Therapy Efficacy Combined With Prostatic Irradiation: The Central Role of Tumor Stage and Radiation Dose

    SciTech Connect

    Williams, Scott; Buyyounouski, Mark; Kestin, Larry; Duchesne, Gillian; Pickles, Tom

    2011-03-01

    Purpose: To evaluate the response of clinically localized prostate cancer to various durations of planned androgen deprivation therapy (ADT) and to investigate subgroups predicting response. Methods and Materials: Data of 3,666 prostate cancer patients treated with either combined ADT and external beam radiotherapy (EBRT) or EBRT alone at four institutions were examined. ADT consisted of neoadjuvant, concurrent, or adjuvant ADT or combinations of these regimens. The primary endpoint was time to biochemical failure (nadir plus 2 ng/ml), assessed from the end of therapy. Factors predictive for the need for ADT were examined with interaction analyses. Results: The impact of increasing ADT duration was nonlinear with, on average, 6 months of adjuvant ADT resulting in a reduction of the risk of biochemical failure by 38% (95% confidence interval [CI], 29%-46%), while 12, 24, and 36 months of ADT resulted in a 58% (95% CI, 47%-67%), 66% (95% CI, 55%-75%), and 66% (95% CI, 51%-77%) relative failure reduction, respectively. Patients with higher T stage cancers and those treated with lower radiation doses had a significantly greater benefit for increasing ADT duration (interaction, p = 0.016 and p = 0.007, respectively). Pretreatment prostate-specific antigen values, Gleason score, age, and risk group did not modify the response to ADT. Conclusions: The known ADT efficacy derived from randomized studies can be generalized to patients with different features, and individual predictions of potential benefit from ADT use and duration may be calculated to aid patient and physician decision making. Tumor stage and radiation dose variations were related to significantly different ADT duration effects. The validity of these predictive factors requires prospective evaluation.

  1. Short-term Androgen-Deprivation Therapy Improves Prostate Cancer-Specific Mortality in Intermediate-Risk Prostate Cancer Patients Undergoing Dose-Escalated External Beam Radiation Therapy

    SciTech Connect

    Zumsteg, Zachary S.; Spratt, Daniel E.; Pei, Xin; Yamada, Yoshiya; Kalikstein, Abraham; Kuk, Deborah; Zhang, Zhigang; Zelefsky, Michael J.

    2013-03-15

    Purpose: We investigated the benefit of short-term androgen-deprivation therapy (ADT) in patients with intermediate-risk prostate cancer (PC) receiving dose-escalated external beam radiation therapy. Methods and Materials: The present retrospective study comprised 710 intermediate-risk PC patients receiving external beam radiation therapy with doses of ≥81 Gy at a single institution from 1992 to 2005, including 357 patients receiving neoadjuvant and concurrent ADT. Prostate-specific antigen recurrence-free survival (PSA-RFS) and distant metastasis (DM) were compared using the Kaplan-Meier method and Cox proportional hazards models. PC-specific mortality (PCSM) was assessed using competing-risks analysis. Results: The median follow-up was 7.9 years. Despite being more likely to have higher PSA levels, Gleason score 4 + 3 = 7, multiple National Comprehensive Cancer Network intermediate-risk factors, and older age (P≤.001 for all comparisons), patients receiving ADT had improved PSA-RFS (hazard ratio [HR], 0.598; 95% confidence interval [CI], 0.435-0.841; P=.003), DM (HR, 0.424; 95% CI, 0.219-0.819; P=.011), and PCSM (HR, 0.380; 95% CI, 0.157-0.921; P=.032) on univariate analysis. Using multivariate analysis, ADT was an even stronger predictor of improved PSA-RFS (adjusted HR [AHR], 0.516; 95% CI, 0.360-0.739; P<.001), DM (AHR, 0.347; 95% CI, 0.176-0.685; P=.002), and PCSM (AHR, 0.297; 95% CI, 0.128-0.685; P=.004). Gleason score 4 + 3 = 7 and ≥50% positive biopsy cores were other independent predictors of PCSM. Conclusions: Short-term ADT improves PSA-RFS, DM, and PCSM in patients with intermediate-risk PC undergoing dose-escalated external beam radiation therapy.

  2. PSA Response to Neoadjuvant Androgen Deprivation Therapy Is a Strong Independent Predictor of Survival in High-Risk Prostate Cancer in the Dose-Escalated Radiation Therapy Era

    SciTech Connect

    McGuire, Sean E.; Lee, Andrew K.; Cerne, Jasmina Z.; Munsell, Mark F.; Levy, Lawrence B.; Kudchadker, Rajat J.; Choi, Seungtaek L.; Nguyen, Quynh N.; Hoffman, Karen E.; Pugh, Thomas J.; Frank, Steven J.; Corn, Paul G.; Logothetis, Christopher J.; Kuban, Deborah A.

    2013-01-01

    Purpose: The aim of the study was to evaluate the prognostic value of prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) prior to dose-escalated radiation therapy (RT) and long-term ADT in high-risk prostate cancer. Methods and Materials: We reviewed the charts of all patients diagnosed with high-risk prostate cancer and treated with a combination of long-term ADT (median, 24 months) and dose-escalated (median, 75.6 Gy) RT between 1990 and 2007. The associations among patient, tumor, and treatment characteristics with biochemical response to neoadjuvant ADT and their effects on failure-free survival (FFS), time to distant metastasis (TDM), prostate cancer-specific mortality (PCSM) and overall survival (OS) were examined. Results: A total of 196 patients met criteria for inclusion. Median follow-up time for patients alive at last contact was 7.0 years (range, 0.5-18.1 years). Multivariate analysis identified the pre-RT PSA concentration (<0.5 vs {>=}0.5 ng/mL) as a significant independent predictor of FFS (P=.021), TDM (P=.009), PCSM (P=.039), and OS (P=.037). On multivariate analysis, pretreatment PSA (iPSA) and African-American race were significantly associated with failure to achieve a pre-RT PSA of <0.5 ng/mL. Conclusions: For high-risk prostate cancer patients treated with long-term ADT and dose-escalated RT, a pre-RT PSA level {>=}0.5 ng/mL after neoadjuvant ADT predicts for worse survival measures. Both elevated iPSA and African-American race are associated with increased risk of having a pre-RT PSA level {>=}0.5 ng/mL. These patients should be considered for clinical trials that test newer, more potent androgen-depleting therapies such as abiraterone and MDV3100 in combination with radiation.

  3. Elucidation of the mechanism of suppressed steroidogenesis during androgen deprivation therapy of prostate cancer patients using a mouse model.

    PubMed

    Taniguchi, H; Katano, T; Nishida, K; Kinoshita, H; Matsuda, T; Ito, S

    2016-09-01

    Androgen deprivation therapy (ADT) is the standard medical approach to the management of prostate cancer. Patients switched from a GnRH antagonist to a GnRH agonist, did not experience a testosterone surge in spite of the occurrence of luteinizing hormone (LH) surge in our protocol of clinical study. To clarify this observation, male mice pre-treated with two different doses of the GnRH antagonist degarelix for 28 days were further administered the GnRH agonist leuprolide or chorionic gonadotropin, and testosterone production of the mice was studied. Serum LH and testosterone levels, the size of Leydig cells, and expression level of steroidogenesis-related genes in the testis were analyzed. Treatment of mice with a high dose of degarelix (0.1 μg/mouse; HDG), but not a low dose (0.05 μg/mouse; LDG), for 28 days reproduced declined steroidogenesis observed in prostate cancer patients during ADT switched from a GnRH antagonist to a GnRH agonist. The size of the Leydig cells in the HDG mice was not significantly different from that in naive mice. Although expression levels of StAR, P450scc, and 17β HSD increased significantly in the LDH testis, those in the HDG testis did not change. Treatment of mice with a high dose of degarelix for 28 days reproduced the decline in steroidogenesis observed in prostate cancer patients during ADT. In this animal model, we demonstrated that initial ADT may inhibit the ability of Leydig cells to produce testosterone by suppressing the expression of genes involved in steroidogenesis, such as StAR, P450scc, and 17βHSD. PMID:27230983

  4. Is Androgen Deprivation Therapy Necessary in All Intermediate-Risk Prostate Cancer Patients Treated in the Dose Escalation Era?

    SciTech Connect

    Castle, Katherine O.; Hoffman, Karen E.; Levy, Lawrence B.; Lee, Andrew K.; Choi, Seungtaek; Nguyen, Quynh N.; Frank, Steven J.; Pugh, Thomas J.; McGuire, Sean E.; Kuban, Deborah A.

    2013-03-01

    Purpose: The benefit of adding androgen deprivation therapy (ADT) to dose-escalated radiation therapy (RT) for men with intermediate-risk prostate cancer is unclear; therefore, we assessed the impact of adding ADT to dose-escalated RT on freedom from failure (FFF). Methods: Three groups of men treated with intensity modulated RT or 3-dimensional conformal RT (75.6-78 Gy) from 1993-2008 for prostate cancer were categorized as (1) 326 intermediate-risk patients treated with RT alone, (2) 218 intermediate-risk patients treated with RT and ≤6 months of ADT, and (3) 274 low-risk patients treated with definitive RT. Median follow-up was 58 months. Recursive partitioning analysis based on FFF using Gleason score (GS), T stage, and pretreatment PSA concentration was applied to the intermediate-risk patients treated with RT alone. The Kaplan-Meier method was used to estimate 5-year FFF. Results: Based on recursive partitioning analysis, intermediate-risk patients treated with RT alone were divided into 3 prognostic groups: (1) 188 favorable patients: GS 6, ≤T2b or GS 3+4, ≤T1c; (2) 71 marginal patients: GS 3+4, T2a-b; and (3) 68 unfavorable patients: GS 4+3 or T2c disease. Hazard ratios (HR) for recurrence in each group were 1.0, 2.1, and 4.6, respectively. When intermediate-risk patients treated with RT alone were compared to intermediate-risk patients treated with RT and ADT, the greatest benefit from ADT was seen for the unfavorable intermediate-risk patients (FFF, 74% vs 94%, respectively; P=.005). Favorable intermediate-risk patients had no significant benefit from the addition of ADT to RT (FFF, 94% vs 95%, respectively; P=.85), and FFF for favorable intermediate-risk patients treated with RT alone approached that of low-risk patients treated with RT alone (98%). Conclusions: Patients with favorable intermediate-risk prostate cancer did not benefit from the addition of ADT to dose-escalated RT, and their FFF was nearly as good as patients with low-risk disease

  5. Prostate-Specific Antigen Halving Time While on Neoadjuvant Androgen Deprivation Therapy Is Associated With Biochemical Control in Men Treated With Radiation Therapy for Localized Prostate Cancer

    SciTech Connect

    Malik, Renuka; Jani, Ashesh B.; Liauw, Stanley L.

    2011-03-15

    Purpose: To assess whether the PSA response to neoadjuvant androgen deprivation therapy (ADT) is associated with biochemical control in men treated with radiation therapy (RT) for prostate cancer. Methods and Materials: In a cohort of men treated with curative-intent RT for localized prostate cancer between 1988 and 2005, 117 men had PSA values after the first and second months of neoadjuvant ADT. Most men had intermediate-risk (45%) or high-risk (44%) disease. PSA halving time (PSAHT) was calculated by first order kinetics. Median RT dose was 76 Gy and median total duration of ADT was 4 months. Freedom from biochemical failure (FFBF, nadir + 2 definition) was analyzed by PSAHT and absolute PSA nadir before the start of RT. Results: Median follow-up was 45 months. Four-year FFBF was 89%. Median PSAHT was 2 weeks. A faster PSA decline (PSAHT {<=}2 weeks) was associated with greater FFBF (96% vs. 81% for a PSAHT >2 weeks, p = 0.0110). Those within the fastest quartile of PSAHTs ({<=} 10 days) achieved a FFBF of 100%. Among high-risk patients, a PSAHT {<=}2 weeks achieved a 4-yr FFBF of 93% vs. 70% for those with PSAHT >2 weeks (p = 0.0508). Absolute PSA nadir was not associated with FFBF. On multivariable analysis, PSAHT (p = 0.0093) and Gleason score (p = 0.0320) were associated with FFBF, whereas T-stage (p = 0.7363) and initial PSA level (p = 0.9614) were not. Conclusions: For men treated with combined ADT and RT, PSA response to the first month of ADT may be a useful criterion for prognosis and treatment modification.

  6. Rapid Conversion of Adolescent MMPI Raw Scores to T Scores Using the HP-67 Programmable Calculator.

    ERIC Educational Resources Information Center

    Hembling, David W.

    1984-01-01

    Used a programmable Hewlett-Packard scientific calculator to rapidly convert raw scores from adolescent MMPI protocols to T scores, scale by scale. The K factor is handled, as needed, automatically. Complete scoring and profiling of the R-form MMPI can be done in less than 10 minutes. (Author/JAC)

  7. Adjunctive Triple Chronotherapy (Combined Total Sleep Deprivation, Sleep Phase Advance, and Bright Light Therapy) Rapidly Improves Mood and Suicidality in Suicidal Depressed Inpatients: An Open Label Pilot Study

    PubMed Central

    Sahlem, Gregory L.; Kalivas, Benjamin; Fox, James B.; Lamb, Kayla; Roper, Amanda; Williams, Emily N.; Williams, Nolan R.; Korte, Jeffrey E.; Zuschlag, Zachary D.; El Sabbagh, Salim; Guille, Constance; Barth, Kelly S.; Uhde, Thomas W.; George, Mark S.; Short, E.Baron

    2014-01-01

    Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N=10, Mean age=44±16.4SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33–36 hours), followed by a three-night sleep phase advance along with four 30-minute sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7±4.2SD at baseline to a mean of 9.4±7.3SD on day five (p=.002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5±8.5SD at baseline to a mean of 7.2±5.5SD on day five (p=.01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed. PMID:25231629

  8. Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: an open label pilot study.

    PubMed

    Sahlem, Gregory L; Kalivas, Benjamin; Fox, James B; Lamb, Kayla; Roper, Amanda; Williams, Emily N; Williams, Nolan R; Korte, Jeffrey E; Zuschlag, Zachary D; El Sabbagh, Salim; Guille, Constance; Barth, Kelly S; Uhde, Thomas W; George, Mark S; Short, E Baron

    2014-12-01

    Previous studies have demonstrated that combined total sleep deprivation (Wake therapy), sleep phase advance, and bright light therapy (Triple Chronotherapy) produce a rapid and sustained antidepressant effect in acutely depressed individuals. To date no studies have explored the impact of the intervention on unipolar depressed individuals with acute concurrent suicidality. Participants were suicidal inpatients (N = 10, Mean age = 44 ± 16.4 SD, 6F) with unipolar depression. In addition to standard of care, they received open label Triple Chronotherapy. Participants underwent one night of total sleep deprivation (33-36 h), followed by a three-night sleep phase advance along with four 30-min sessions of bright light therapy (10,000 lux) each morning. Primary outcome measures included the 17 item Hamilton depression scale (HAM17), and the Columbia Suicide Severity Rating Scale (CSSRS), which were recorded at baseline prior to total sleep deprivation, and at protocol completion on day five. Both HAM17, and CSSRS scores were greatly reduced at the conclusion of the protocol. HAM17 scores dropped from a mean of 24.7 ± 4.2 SD at baseline to a mean of 9.4 ± 7.3 SD on day five (p = .002) with six of the ten individuals meeting criteria for remission. CSSRS scores dropped from a mean of 19.5 ± 8.5 SD at baseline to a mean of 7.2 ± 5.5 SD on day five (p = .01). The results of this small pilot trial demonstrate that adjunctive Triple Chronotherapy is feasible and tolerable in acutely suicidal and depressed inpatients. Limitations include a small number of participants, an open label design, and the lack of a comparison group. Randomized controlled studies are needed. PMID:25231629

  9. Prevention of Gynecomastia and Breast Pain Caused by Androgen Deprivation Therapy in Prostate Cancer: Tamoxifen or Radiotherapy?

    SciTech Connect

    Arruda Viani, Gustavo; Bernardes da Silva, Lucas Godoi; Stefano, Eduardo Jose

    2012-07-15

    Purpose: To determine, in a meta-analysis, whether gynecomastia and breast pain rates in men with prostate cancer treated with androgen deprivation therapy (ADT) are reduced if treated with prophylactic radiotherapy (RT) or tamoxifen (TMX). Methods and Materials: The MEDLINE, EMBASE, CANCERLIT, and Cochrane Library databases, as well as proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing RT or TMX with observation for men with prostate cancer using ADT. Results: Six RCTs (three RT trials and three TMX trials, N = 777 patients total) were identified that met the study criteria. Pooled results from these RCTs comparing RT vs. observation showed a significant reduction in the incidence of gynecomastia and breast pain rates in patients treated with RT (odds ratio [OR] = 0.21, 95% confidence interval [CI] = 0.12-0.37, p < 0.0001, and OR = 0.34, 95% CI 0.20-0.57, p < 0.0001, respectively). Use of RT resulted in an absolute risk reduction (ARR) of 29.4% and 19.9%, with a number needed to treat (NNT) of 3.4 and 5 to avoid one case of gynecomastia and breast pain, respectively. Pooled results from trials comparing TMX vs. observation showed a statistical benefit for breast pain and gynecomastia in favor of TMX arms (OR = 0.04, 95% CI = 0.02-0.08, p < 0.0001 and OR = 0.07, 95% CI = 0.0-0.14, p < 0.00001). TMX resulted in an ARR = 64.1% and 47.6%, with an NNT of 1.56 and 2.1 to avoid one case of gynecomastia and breast pain, respectively. Considering adverse effects, TMX was 6 times more adverse effects than RT. Conclusions: Our data have shown that both TMX and RT prevented gynecomastia and breast pain in patients with prostate cancer receiving ADT for prostate cancer. Although TMX was two times more effective in preventing gynecomastia, RT should represent an effective and safe treatment option, to take into account mainly in patients with cardiovascular risk factors or thrombotic diathesis.

  10. Endurance training improves insulin sensitivity and body composition in prostate cancer patients treated with androgen deprivation therapy.

    PubMed

    Hvid, Thine; Winding, Kamilla; Rinnov, Anders; Dejgaard, Thomas; Thomsen, Carsten; Iversen, Peter; Brasso, Klaus; Mikines, Kari J; van Hall, Gerrit; Lindegaard, Birgitte; Solomon, Thomas P J; Pedersen, Bente K

    2013-10-01

    Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine men undergoing ADT for prostate cancer and ten healthy men with normal testosterone levels underwent 12 weeks of endurance training. Primary endpoints were insulin sensitivity (euglycemic-hyperinsulinemic clamps with concomitant glucose-tracer infusion) and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO2max (ml(O2)/min per kg) by 11 and 13% in the patients and controls respectively (P<0.0001). The patients and controls demonstrated an increase in peripheral tissue insulin sensitivity of 14 and 11% respectively (P<0.05), with no effect on hepatic insulin sensitivity (P=0.32). Muscle protein content of GLUT4 (SLC2A4) and total AKT (AKT1) was also increased in response to the training (P<0.05 and P<0.01 respectively). Body weight (P<0.0001) and whole-body fat mass (FM) (P<0.01) were reduced, while lean body mass (P=0.99) was unchanged. Additionally, reductions were observed in abdominal (P<0.01), subcutaneous (P<0.05), and visceral (P<0.01) FM amounts. The concentrations of plasma markers of systemic inflammation were unchanged in response to the training. No group × time interactions were observed, except for thigh intermuscular adipose tissue (IMAT) (P=0.01), reflecting a significant reduction in the amount of IMAT in the controls (P<0.05) not observed in the patients (P=0.64). In response to endurance training, ADT-treated prostate cancer patients exhibited improved insulin sensitivity and body composition to a similar degree as eugonadal men. PMID:23744766

  11. Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

    SciTech Connect

    Sharma, Navesh K.; Li Tianyu; Chen, David Y.; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2011-06-01

    Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; {>=}6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. {>=}6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

  12. Responder Analysis of the Effects of Denosumab on Bone Mineral Density in Men Receiving Androgen Deprivation Therapy for Prostate Cancer

    PubMed Central

    Egerdie, Blair; Saad, Fred; Smith, Matthew R; Tammela, Teuvo LJ; Heracek, Jiri; Sieber, Paul; Ke, Chunlei; Leder, Benjamin; Dansey, Roger; Goessl, Carsten

    2013-01-01

    Background Men with prostate cancer are at risk of experiencing accelerated bone loss and fractures as a result of androgen deprivation therapy (ADT). Objective We evaluated the effects of denosumab, a fully human monoclonal antibody against RANKL, on preservation of BMD at 3 key skeletal sites (lumbar spine [LS], femoral neck [FN], and total hip [TH]) and the distal radius at 36 months both by responder category and individual responses in a waterfall plot analysis. Design, Setting, and Participants This phase 3, randomized, double-blind study of men with non-metastatic prostate cancer receiving ADT investigated the effects of denosumab on bone mineral density (BMD) and fractures. Patients were treated for 36 months. Intervention Subcutaneous denosumab 60 mg (n=734) or placebo (n=734) every 6 months for up to 36 months. Patients were instructed to take supplemental Calcium and vitamin D. Measurements Primary outcome measure: The percentage change from baseline to month 36 in LS, FN, and TH BMD was measured by dual energy x-ray absorptiometry. BMD at the distal 1/3 radius at 36 months was measured in a sub-study of 309 patients. Results and Limitations At 36 months, significantly more patients in the denosumab arm had increases of >3% BMD from baseline at each site studied compared with placebo (LS, 78% vs 17%; TH, 48% vs 6%; FN, 48% vs 13%; distal 1/3 radius, 40% vs 7%). The percentage of denosumab patients with bone loss at all 3 key BMD sites at month 36 was 1%, as opposed to 42% in placebo arm. At 36 months 69% of denosumab-treated patients had BMD increases at all three sites (LS, TH or FN) compared with 8% of placebo-treated patients. Lower baseline BMD was associated with higher magnitude lumbar spine, femoral neck, and total hip BMD responses to denosumab. Conclusions In men with prostate cancer receiving ADT significantly higher BMD response rates were observed with denosumab vs. placebo. Trial Registration This study is registered with Clinical

  13. Causes of Mortality After Dose-Escalated Radiation Therapy and Androgen Deprivation for High-Risk Prostate Cancer

    SciTech Connect

    Tendulkar, Rahul D.; Hunter, Grant K.; Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Abdel-Wahab, May; Stephenson, Andrew J.; Klein, Eric A.; Mahadevan, Arul; Kupelian, Patrick A.

    2013-09-01

    Purpose: Men with high-risk prostate cancer have other competing causes of mortality; however, current risk stratification schema do not account for comorbidities. We aim to identify the causes of death and factors predictive for mortality in this population. Methods and Materials: A total of 660 patients with high-risk prostate cancer were treated with definitive high-dose external beam radiation therapy (≥74 Gy) and androgen deprivation (AD) between 1996 and 2009 at a single institution. Cox proportional hazards regression analysis was conducted to determine factors predictive of survival. Results: The median radiation dose was 78 Gy, median duration of AD was 6 months, and median follow-up was 74 months. The 10-year overall survival (OS) was 60.6%. Prostate cancer was the leading single cause of death, with 10-year mortality of 14.1% (95% CI 10.7-17.6), compared with other cancers (8.4%, 95% CI 5.7-11.1), cardiovascular disease (7.3%, 95% CI 4.7-9.9), and all other causes (10.4%, 95% CI 7.2-13.6). On multivariate analysis, older age (HR 1.55, P=.002) and Charlson comorbidity index score (CS) ≥1 (HR 2.20, P<.0001) were significant factors predictive of OS, whereas Gleason score, T stage, prostate-specific antigen, duration of AD, radiation dose, smoking history, and body mass index were not. Men younger than 70 years of age with CS = 0 were more likely to die of prostate cancer than any other cause, whereas older men or those with CS ≥1 more commonly suffered non-prostate cancer death. The cumulative incidences of prostate cancer-specific mortality were similar regardless of age or comorbidities (P=.60). Conclusions: Men with high-risk prostate cancer are more likely to die of causes other than prostate cancer, except for the subgroup of men younger than 70 years of age without comorbidities. Only older age and presence of comorbidities significantly predicted for OS, whereas prostate cancer- and treatment-related factors did not.

  14. MEDICAL "DEPRIVATION."

    ERIC Educational Resources Information Center

    SUCHMAN, EDWARD A.

    THE SOCIAL AND MEDICAL PROBLEM TODAY HAS SHIFTED FROM PROVIDING FOR THE EMERGENCY MEDICAL NEEDS OF THE INDIGENT SICK TO RAISING THE LEVEL OF LOWER CLASS PARTICIPATION IN THE BENEFITS OF MODERN MEDICINE. GREATER ATTENTION IS BEING FOCUSED ON MEDICAL DEPRIVATION SUFFERED BY LARGE SEGMENTS OF THE POPULATION WHO DO NOT SHARE EQUALLY IN MEDICAL…

  15. Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway.

    PubMed

    Ardiani, Andressa; Gameiro, Sofia R; Kwilas, Anna R; Donahue, Renee N; Hodge, James W

    2014-10-15

    Despite recent advances in diagnosis and management, prostrate cancer remains the second most common cause of death from cancer in American men, after lung cancer. Failure of chemotherapies and hormone-deprivation therapies is the major cause of death in patients with castration-resistant prostate cancer (CRPC). Currently, the androgen inhibitors enzalutamide and abiraterone are approved for treatment of metastatic CRPC. Here we show for the first time that both enzalutamide and abiraterone render prostate tumor cells more sensitive to T cell-mediated lysis through immunogenic modulation, and that these immunomodulatory activities are androgen receptor (AR)-dependent. In studies reported here, the NAIP gene was significantly down-regulated in human prostate tumor cells treated in vitro and in vivo with enzalutamide. Functional analysis revealed that NAIP played a critical role in inducing CTL sensitivity. Amplification of AR is a major mechanism of resistance to androgen-deprivation therapy (ADT). Here, we show that enzalutamide enhances sensitivity to immune-mediated killing of prostate tumor cells that overexpress AR. The immunomodulatory properties of enzalutamide and abiraterone provide a rationale for their use in combination with immunotherapeutic agents in CRPC, especially for patients with minimal response to enzalutamide or abiraterone alone, or for patients who have developed resistance to ADT. PMID:25344864

  16. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated With Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease

    SciTech Connect

    Stenmark, Matthew H.; Blas, Kevin; Halverson, Schuyler; Sandler, Howard M.; Feng, Felix Y.; Hamstra, Daniel A.

    2011-11-15

    Purpose: To analyze prognostic factors in patients with high-risk prostate cancer treated with dose-escalated external-beam radiation therapy (EBRT) and androgen deprivation (ADT). Methods and Materials: Between 1998 and 2008 at University of Michigan Medical Center, 718 men were consecutively treated with EBRT to at least 75 Gy. Seven definitions of high-risk prostate cancer, applying to 11-33% of patients, were evaluated. Biochemical failure (BF), salvage ADT use, metastatic progression, and prostate cancer-specific mortality (PCSM) were estimated by the Kaplan-Meier method and Cox proportional hazards regression. Results: Each high-risk definition was associated with increased BF (hazard ratio [HR] 2.8-3.9, p < 0.0001), salvage ADT use (HR 3.9-6.3, p < 0.0001), metastasis (HR 3.7-6.6, p < 0.0001), and PCSM (HR 3.7-16.2, p < 0.0001). Furthermore, an increasing number of high-risk features predicted worse outcome. Adjuvant ADT yielded significant reductions in both metastases (HR 0.19-0.38, p < 0.001) and PCSM (HR 0.38-0.50, p < 0.05) for all high-risk definitions (with the exception of clinical Stage T3-4 disease) but improved BF only for those with elevated Gleason scores (p < 0.03, HR 0.25-0.48). When treated with ADT and dose-escalated EBRT, patients with Gleason scores 8 to 10, without other high-risk features, had 8-year freedom from BF of 74%, freedom from distant metastases of 93%, and cause-specific survival of 92%, with salvage ADT used in 16% of patients. Conclusion: Adjuvant ADT results in a significant improvement in clinical progression and PCSM across multiple definitions of high-risk disease even with dose-escalated EBRT. There is a subset of patients, characterized by multiple high-risk features or the presence of Gleason Pattern 5, who remain at significant risk for metastasis and PCSM despite current treatment.

  17. Rapid conversion of adolescent MMPI raw scores to T scores using the HP-67 programmable calculator.

    PubMed

    Hembling, D W

    1984-01-01

    Used a programmable Hewlett-Packard scientific calculator (HP-67, 97, 41C, 41CV) to rapidly convert raw scores from adolescent MMPI protocols to T scores, scale by scale. The K factor is handled, as needed, automatically. The program is stored on one side of a standard HP magnetic card. The norm data for adolescents (or optionally any other group) in the age groups less than 15, 15, 16, and 17 occupy two sides per sex per age group of eight magnetic data cards. Complete scoring and profiling of the R-form MMPI can be done in less than 10 minutes. PMID:6547731

  18. Androgen deprivation induces phenotypic plasticity and promotes resistance to molecular targeted therapy in a PTEN-deficient mouse model of prostate cancer.

    PubMed

    De Velasco, Marco A; Tanaka, Motoyoshi; Yamamoto, Yutaka; Hatanaka, Yuji; Koike, Hiroyuki; Nishio, Kazuto; Yoshikawa, Kazuhiro; Uemura, Hirotsugu

    2014-09-01

    Castration-resistant prostate cancer is an incurable heterogeneous disease that is characterized by a complex multistep process involving different cellular and biochemical changes brought on by genetic and epigenetic alterations. These changes lead to the activation or overexpression of key survival pathways that also serve as potential therapeutic targets. Despite promising preclinical results, molecular targeted therapies aimed at such signaling pathways have so far been dismal. In the present study, we used a PTEN-deficient mouse model of prostate cancer to show that plasticity in castration-resistant tumors promotes therapeutic escape. Unlike castration-naïve tumors which depend on androgen receptor and PI3K/AKT signal activation for growth and survival, castration-resistant tumors undergo phenotypic plasticity leading to increased intratumoral heterogeneity. These tumors attain highly heterogeneous phenotypes that are characterized by cancer cells relying on alternate signal transduction pathways for growth and survival, such as mitogen-activated protein kinase and janus kinase/signal transducer and activator of transcription, and losing their dependence on PI3K signaling. These features thus enabled castration-resistant tumors to become insensitive to the therapeutic effects of PI3K/AKT targeted therapy. Overall, our findings provide evidence that androgen deprivation drives phenotypic plasticity in prostate cancer cells and implicate it as a crucial contributor to therapeutic resistance in castration-resistant prostate cancer. Therefore, incorporating intratumoral heterogeneity in a dynamic tumor model as a part of preclinical efficacy determination could improve prediction for response and provide better rationale for the development of more effective therapies. PMID:24986896

  19. Relationship between prostate volume changes and treatment duration of neoadjuvant androgen deprivation during intensity-modulated radiation therapy for Japanese patients with prostate cancer

    PubMed Central

    Tomida, Masashi; Okudaira, Kuniyasu; Kamomae, Takeshi; Oguchi, Hiroshi; Miyake, Yoshikazu; Yoneda, Kazuo; Itoh, Yoshiyuki

    2016-01-01

    ABSTRACT The application of neoadjuvant androgen deprivation (NAD) in prostate cancer leads to a reduction in prostate volume, and the trends in volume reduction differ according to the treatment duration of NAD. A reduction in volume during external beam radiation therapy may lead to the exposure of normal tissues to an unexpected dose. In fact, prostate volume reductions have primarily been reported in European and American institutions. Although the prostate volume of Japanese patients is known to be small, the trends in prostate volume change during radiation therapy remain unclear. In the present study, we aimed to evaluate the changes in prostate volume of Japanese patients during intensity-modulated radiation therapy (IMRT) with NAD. Nineteen Japanese patients with prostate cancer underwent IMRT with NAD. Kilovoltage computed tomography (CT) images were obtained for treatment planning and verification of the treatment position for each treatment fraction. The patients were divided into 3 groups based on the duration of NAD, as follows: NAD < 3 months (short NAD: S-NAD), 3 months ≤ NAD < 6 months (middle NAD: M-NAD), and NAD ≥ 6 months (long NAD: L-NAD). The prostate volume reductions at the 36th treatment fraction, relative to the planning CT, were 7.8%, 2.0%, and 1.7% for the S-NAD, M-NAD, and L-NAD groups, respectively. Prostate volume shrunk greater in the S-NAD group than in the M-NAD and L-NAD groups; this finding was consistent with those of previous studies. The prostate volume changes in Japanese patients were smaller compared to those in European and American patients. PMID:27578915

  20. Relationship between prostate volume changes and treatment duration of neoadjuvant androgen deprivation during intensity-modulated radiation therapy for Japanese patients with prostate cancer.

    PubMed

    Tomida, Masashi; Okudaira, Kuniyasu; Kamomae, Takeshi; Oguchi, Hiroshi; Miyake, Yoshikazu; Yoneda, Kazuo; Itoh, Yoshiyuki

    2016-08-01

    The application of neoadjuvant androgen deprivation (NAD) in prostate cancer leads to a reduction in prostate volume, and the trends in volume reduction differ according to the treatment duration of NAD. A reduction in volume during external beam radiation therapy may lead to the exposure of normal tissues to an unexpected dose. In fact, prostate volume reductions have primarily been reported in European and American institutions. Although the prostate volume of Japanese patients is known to be small, the trends in prostate volume change during radiation therapy remain unclear. In the present study, we aimed to evaluate the changes in prostate volume of Japanese patients during intensity-modulated radiation therapy (IMRT) with NAD. Nineteen Japanese patients with prostate cancer underwent IMRT with NAD. Kilovoltage computed tomography (CT) images were obtained for treatment planning and verification of the treatment position for each treatment fraction. The patients were divided into 3 groups based on the duration of NAD, as follows: NAD < 3 months (short NAD: S-NAD), 3 months ≤ NAD < 6 months (middle NAD: M-NAD), and NAD ≥ 6 months (long NAD: L-NAD). The prostate volume reductions at the 36th treatment fraction, relative to the planning CT, were 7.8%, 2.0%, and 1.7% for the S-NAD, M-NAD, and L-NAD groups, respectively. Prostate volume shrunk greater in the S-NAD group than in the M-NAD and L-NAD groups; this finding was consistent with those of previous studies. The prostate volume changes in Japanese patients were smaller compared to those in European and American patients. PMID:27578915

  1. 5α-reductase Inhibition Coupled with Short Off Cycles Increases Survival in the LNCaP Xenograft Prostate Tumor Model on Intermittent Androgen Deprivation Therapy

    PubMed Central

    Pascal, Laura E.; Masoodi, Khalid Z.; O’Malley, Katherine J.; Shevrin, Daniel; Gingrich, Jeffrey R.; Parikh, Rahul A.; Wang, Zhou

    2014-01-01

    Purpose Intermittent androgen deprivation therapy (IADT) for patients with PSA progression after treatment for localized prostate cancer is an alternative to the standard continuous ADT. IADT allows for the recovery of testosterone during off-cycles to stimulate regrowth and differentiation of the regressed prostate tumor in order to lessen the side effects of continuous ADT and potentially prolong survival. Previously, IADT coupled with finasteride was shown to prolong survival of animals bearing androgen-sensitive prostate tumors when off-cycle duration was not prolonged and fixed at 10–14 days. Regressed prostate tumor xenografts with testosterone replacement were initially responsive to 5α-reductase inhibition, but resumed growth after several days in the animal models. 5α-reductase inhibition in shorter off-cycles of testosterone recovery could maximize tumor growth inhibition during IADT and perhaps increase survival. Materials and Methods The LNCaP xenograft tumor model was utilized to evaluate the effectiveness of short off-cycles of 4 days coupled with 5α-reductase inhibition on IADT on survival and tumor regrowth. Results Dutasteride inhibited initial testosterone-induced tumor regrowth during both the first and second off-cycle and significantly increased survival. Conclusions These results further support the potential for IADT combined with 5α-reductase inhibition to improve survival in prostate cancer patients when off cycle durations are short or very short. PMID:25444984

  2. Development of UK guidance on the management of erectile dysfunction resulting from radical radiotherapy and androgen deprivation therapy for prostate cancer

    PubMed Central

    White, I D; Wilson, J; Aslet, P; Baxter, A B; Birtle, A; Challacombe, B; Coe, J; Grover, L; Payne, H; Russell, S; Sangar, V; Van As, N; Kirby, M

    2015-01-01

    Aim To develop a management strategy (rehabilitation programme) for erectile dysfunction (ED) after radiotherapy (RT) or androgen deprivation therapy (ADT) for prostate cancer that is suitable for use in a UK NHS healthcare context. Methods PubMed literature searches of ED management in this patient group together with a survey of 28 experts in the management of treatment-induced ED from across the UK were conducted. Results Data from 19 articles and completed questionnaires were collated. The findings discussed in this article confirm that RT/ADT for prostate cancer can significantly impair erectile function. While many men achieve erections through PDE5-I use, others need combined management incorporating exercise and lifestyle modifications, psychosexual counselling and other erectile aids. This article offers a comprehensive treatment algorithm to manage patients with ED associated with RT/ADT. Conclusion Based on published research literature and survey analysis, recommendations are proposed for the standardisation of management strategies employed for ED after RT/ADT. In addition to implementing the algorithm, understanding the rationale for the type and timing of ED management strategies is crucial for clinicians, men and their partners. PMID:25283500

  3. What do urologists think patients need to know when starting on androgen deprivation therapy? The perspective from Canada versus countries with lower gross domestic product

    PubMed Central

    Rot, Irena; Wassersug, Richard J.

    2016-01-01

    Background Androgen deprivation therapy (ADT) side effects are numerous and negatively impact prostate cancer patients’ quality of life. There is considerable discrepancy though among Canadian urologists regarding what ADT side effects and side effect management strategies. Little is known about global differences in ADT patient education. Methods International respondents were recruited via online posting and at an international urology conference. Hypotheses suggest that economic and cultural differences influence patient education practices; therefore, international respondents were divided into 3 categories (high, medium, and low gross domestic product). Results No differences were found between responses from Canadian urologists and high GDP countries. Compared to responses from low GDP countries, Canadian urologists are more likely to endorse informing patients about: osteoporosis, loss of muscle mass, weight gain, fatigue/sleep disturbance, relationship changes, cognitive changes, and loss of body hair. Infertility was the only side effect more often disclosed by urologists in low GDP counties. Recommended management strategies for hot flashes are more likely to be pharmaceutical in Canada, and behavioral in low GDP countries. Management strategies for gynecomastia are emphasized more in low GDP countries. Physical exercise is endorsed consistently more often by Canadian urologists. Conclusions ADT educational practices vary greatly between Canada and lower GDP countries. Factors that could contribute to differences include economics (e.g., ADT drug costs), differences in side effect presentation due to different ADT drugs used, racial differences in perceived side effect burden, disease status at ADT commencement, and cultural differences in patient-physician shared-decision making. PMID:27141453

  4. Mortality, cardiovascular risk, and androgen deprivation therapy for prostate cancer: A systematic review with direct and network meta-analyses of randomized controlled trials and observational studies

    PubMed Central

    Scailteux, Lucie-Marie; Naudet, Florian; Alimi, Quentin; Vincendeau, Sébastien; Oger, Emmanuel

    2016-01-01

    Abstract Androgen deprivation therapy (ADT) is a cornerstone therapy for advanced prostate cancer (PCa). We hypothesized that cardiovascular (CV) risk is different across the various ADT modalities to compare their effects on CV morbidity and mortality, and all-cause mortality in patients with PCa. To investigate more in depth potential CV risk heterogeneity focusing on coronary (main outcome) and cerebrovascular risk, CV, and overall mortality. We performed a Medline and Embase query, without language restriction, since 1950 up to July 2014. We included randomized controlled trials (RCTs) and observational studies providing that they compared at least 1 ADT modality to another one or to placebo and they gave data on CV event or all-cause mortality. Sixty-eight studies out of 3419 met our eligibility criteria. Eleven observational studies were analyzed. Direct meta-analyses showed that antiandrogen was associated with a 30% decrease risk for myocardial infarction (MI) compared to GnRH agonists (RR, 0.70 [0.54–0.91]); combined androgen blockade (CAB) was associated with a 10% increase risk for stroke when compared to antiandrogen (RR, 1.10 [1.02–1.19]). With regard to RCTs, 57 were included: direct meta-analyses suggested that CAB was associated with a 10% decrease of all-cause mortality when compared to GnRH agonist (RR, 0.90 [0.82–1.00]). Network analysis could only be performed for all-cause mortality and it remains difficult to disentangle benefit (positive impact on cancer survival) and risk (including CV risk). The impact of the ADT modalities on CV morbidity remains difficult to quantify and more detailed prospective collection is required. Registration: PROSPERO, CRD42014010598. PMID:27310974

  5. Androgen Deprivation Therapy Does Not Impact Cause-Specific or Overall Survival in High-Risk Prostate Cancer Managed With Brachytherapy and Supplemental External Beam

    SciTech Connect

    Merrick, Gregory S. . E-mail: gmerrick@urologicresearchinstitute.org; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A.; Adamovich, Edward; Lief, Jonathan

    2007-05-01

    Purpose: To determine cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in high-risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Methods and Materials: Between April 1995 and July 2002, 204 patients with high-risk prostate cancer (Gleason score {>=}8 or prostate-specific antigen [PSA] >20 ng/mL or clinical stage {>=}T2c) underwent brachytherapy. Median follow-up was 7.0 years. The bPFS was defined by a PSA {<=}0.40 ng/mL after nadir. Multiple clinical, treatment, and dosimetric parameters were evaluated for the impact on survival. Results: The 10-year CSS, bPFS, and OS were 88.9%, 86.6%, and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naive, ADT {<=}6 months, and ADT >6 month cohorts (79.7% vs. 95.% vs. 89.9%, p = 0.032). Androgen deprivation therapy (ADT) did not impact CSS or OS. For bPFS patients, the median posttreatment PSA was <0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS, whereas percent positive biopsies and duration of ADT best predicted for bPFS. The OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died, with 26 of the deaths from cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. Conclusions: The ADT improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact OS.

  6. Upfront Androgen Deprivation Therapy With Salvage Radiation May Improve Biochemical Outcomes in Prostate Cancer Patients With Post-Prostatectomy Rising PSA

    SciTech Connect

    Jang, Joanne W.; Hwang, Wei-Ting; Guzzo, Thomas J.; Wein, Alan J.; Haas, Naomi B.; Both, Stefan; Vapiwala, Neha

    2012-08-01

    Purpose: The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT. Methods and Materials: Of nearly 2,000 post-prostatectomy patients, we reviewed the medical records of 191 patients who received salvage RT at University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Security Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT. Results: One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. Median follow-up was 5.4 years. Patients who received combined ADT and salvage RT were younger, had higher pathologic Gleason scores, and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic nodal irradiation compared with patients who received salvage RT alone. Patients who received combined therapy had improved biochemical progression-free survival (bPFS) compared with patients who received RT alone (p = 0.048). For patients with pathologic Gleason scores {<=}7, combined RT and ADT resulted in significantly improved bPFS compared to RT alone (p = 0.013). Conclusions: These results suggest that initiating ADT during salvage RT in the post-prostatectomy setting may improve bPFS compared with salvage RT alone. However, prospective randomized data are necessary to definitively determine whether hormonal manipulation should be used with salvage RT. Furthermore, the optimal nature and duration of ADT and the patient subgroups in

  7. A Preliminary Attempt at Teaching Abstract Mathematics to Freshmen with an A.C.T. Score of Less Than 15.

    ERIC Educational Resources Information Center

    Schremmer, A. G.

    This experiment attempted to teach abstract mathematics fo college freshmen with A.C.T. scores less than 15 in a three semester terminal course sequence. The course content included a formal mathematical language, set theory, Boolean Algebra, relations and functions, operations, cardinals and ordinals, the rational numbers, and college algebra.…

  8. Effect of Whole Pelvic Radiotherapy for Patients With Locally Advanced Prostate Cancer Treated With Radiotherapy and Long-Term Androgen Deprivation Therapy

    SciTech Connect

    Mantini, Giovanna; Tagliaferri, Luca; Mattiucci, Gian Carlo; Balducci, Mario; Frascino, Vincenzo; Dinapoli, Nicola; Di Gesu, Cinzia; Ippolito, Edy; Morganti, Alessio G.; Cellini, Numa

    2011-12-01

    Purpose: To evaluate the effect of whole pelvic radiotherapy (WPRT) in prostate cancer patients treated with RT and long-term (>1 year) androgen deprivation therapy (ADT). Methods and materials: Prostate cancer patients with high-risk features (Stage T3-T4 and/or Gleason score {>=}7 and/or prostate-specific antigen level {>=}20 ng/mL) who had undergone RT and long-term ADT were included in the present analysis. Patients with bowel inflammatory disease, colon diverticula, and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy (PORT). Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels (15%, 20%, 25%, and 30%). Biochemical disease-free survival (bDFS) was analyzed in each group according to the RT type (WPRT or PORT). Results: A total of 358 patients treated between 1994 and 2007 were included in the analysis (46.9% with WPRT and 53.1% with PORT). The median duration of ADT was 24 months (range, 12-38). With a median follow-up of 52 months (range, 20-150), the overall 4-year bDFS rate was 90.5%. The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT (90.4% vs. 90.5%; p = NS). However, in the group of patients with the greatest nodal risk (>30%), a significant bDFS improvement was recorded for the patients who had undergone WPRT (p = .03). No differences were seen in acute toxicity among the patients treated with WPRT or PORT. The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT (p = NS). Conclusions: Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement (>30%), although a definitive recommendation should be confirmed by a randomized trial.

  9. Lack of Benefit for the Addition of Androgen Deprivation Therapy to Dose-Escalated Radiotherapy in the Treatment of Intermediate- and High-Risk Prostate Cancer

    SciTech Connect

    Krauss, Daniel; Kestin, Larry; Ye, Hong; Brabbins, Donald; Ghilezan, Michel; Gustafson, Gary; Vicini, Frank; Martinez, Alvaro

    2011-07-15

    Purpose: Assessment of androgen deprivation therapy (ADT) benefits for prostate cancer treated with dose-escalated radiotherapy (RT). Methods and Materials: From 1991 to 2004, 1,044 patients with intermediate- (n = 782) or high-risk (n = 262) prostate cancer were treated with dose-escalated RT at William Beaumont Hospital. Patients received external-beam RT (EBRT) alone, brachytherapy (high or low dose rate), or high dose rate brachytherapy plus pelvic EBRT. Intermediate-risk patients had Gleason score 7, prostate-specific antigen (PSA) 10.0-19.9 ng/mL, or Stage T2b-T2c. High-risk patients had Gleason score 8-10, PSA {>=}20, or Stage T3. Patients were additionally divided specifically by Gleason score, presence of palpable disease, and PSA level to further define subgroups benefitting from ADT. Results: Median follow-up was 5 years; 420 patients received ADT + dose-escalated RT, and 624 received dose-escalated RT alone. For all patients, no advantages in any clinical endpoints at 8 years were associated with ADT administration. No differences in any endpoints were associated with ADT administration based on intermediate- vs. high-risk group or RT modality when analyzed separately. Patients with palpable disease plus Gleason {>=}8 demonstrated improved clinical failure rates and a trend toward improved survival with ADT. Intermediate-risk patients treated with brachytherapy alone had improved biochemical control when ADT was given. Conclusion: Benefits of ADT in the setting of dose-escalated RT remain poorly defined. This question must continue to be addressed in prospective study.

  10. Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the ‘FC Prostate’ randomized controlled trial

    PubMed Central

    2013-01-01

    Background Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The ‘Football Club (FC) Prostate’ study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. Methods/Design Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2–3 times/week for 45–60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. Discussion The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. Trial

  11. Long-term androgen deprivation increases Grade 2 and higher late morbidity in prostate cancer patients treated with three-dimensional conformal radiation therapy

    SciTech Connect

    Feigenberg, Steven J. . E-mail: S_Feigenberg@fccc.edu; Hanlon, Alexandra L.; Horwitz, Eric M.; Uzzo, Robert G.; Eisenberg, Debra; Pollack, Alan

    2005-06-01

    Purpose: To determine whether the use of androgen deprivation (AD) increases late morbidity when combined with high-dose three-dimensional conformal radiation therapy (3D-CRT). Methods and materials: Between May 1989 and November 1998, 1,204 patients were treated for prostate cancer with 3D-CRT to a median dose of 74 Gy. Patients were evaluated every 3-6 months. No AD was given to 945 patients, whereas 140 and 119 patients, respectively, received short-term AD (STAD; {<=}6 months) and long-term AD (LTAD; > 6 months). Radiation morbidity was graded according to the Fox Chase modification of the Late Effects Normal Tissue Task Force late morbidity scale. Covariates in the multivariate analysis (MVA) included age, history of diabetes mellitus, prostate-specific antigen (PSA) level, Gleason score, T category, RT field size, total RT dose, use of rectal shielding, and AD status (no AD vs. STAD vs. LTAD). Results: The only independent predictor for Grade 2 or higher genitourinary (GU) morbidity in the MVA was the use of AD (p = 0.0065). The 5-year risk of Grade 2 or higher GU morbidity was 8% for no AD, 8% for STAD, and 14% for LTAD (p = 0.02). Independent predictors of Grade 2 or higher gastrointestinal (GI) morbidity in the MVA were the use of AD (p = 0.0079), higher total radiation dose (p < 0.0001), the lack of a rectal shield (p = 0.0003), and older age (p = 0.0009). The 5-year actuarial risk of Grade 2 or higher GI morbidity was 17% for no AD vs. 18% for STAD and 26% for LTAD (p = 0.017). Conclusions: The use of LTAD seems to significantly increase the risk of both GU and GI morbidity for patients treated with 3D-CRT.

  12. Impact of pre-treatment prostate tissue androgen content on the prediction of castration-resistant prostate cancer development in patients treated with primary androgen deprivation therapy.

    PubMed

    Shibata, Y; Suzuki, K; Arai, S; Miyoshi, Y; Umemoto, S; Masumori, N; Kamiya, N; Ichikawa, T; Kitagawa, Y; Mizokami, A; Sugimura, Y; Nonomura, N; Sakai, H; Honma, S; Kubota, Y

    2013-05-01

    Great advances in tissue androgen analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) have made it possible to evaluate the tissue androgen content from a single needle prostate biopsy specimen. In this study, we investigated if pre-treatment androgen content in prostate biopsy specimens could predict their response to primary androgen deprivation therapy (ADT) and future castration-resistant prostate cancer (CRPC). One-hundred and sixty-five prostate cancer patients who received primary ADT were enrolled. They had received multiple core prostate needle biopsy at diagnosis, and an additional one needle biopsy specimen was obtained for tissue androgen determination using LC-MS/MS. The patients' prostate specific antigen (PSA) values were periodically followed during the treatment and patients were determined to have CRPC when their PSA value increased continuously to 25% above the nadir and a 2.0 ng/mL increase. A significant correlation was found between PSA value decline velocity (PSA half-time) after ADT and pre-ADT tissue androgen content. Twenty-three patients were determined to have CRPC. These CRPC patients had a significantly high concentration of tissue T (p < 0.01) and low concentration of tissue 5α-dihydrotestosterone (DHT) (p < 0.01), resulting in a higher tissue T/DHT ratio (p < 0.001). A multivariate Cox proportional hazard model revealed the pre-ADT tissue T/DHT ratio and Gleason score as independent predictors for CRPC development. By using the two statistically significant variables, the relative risk of CRPC development could be calculated. The results of this study suggest that the evaluation of prostate androgen content in a single needle biopsy specimen may be useful to predict future CRPC development after primary ADT. Further studies are required for the clinical application of T/DHT ratio evaluation. PMID:23444052

  13. Group-based exercise in daily clinical practice to improve physical fitness in men with prostate cancer undergoing androgen deprivation therapy: study protocol

    PubMed Central

    Østergren, Peter; Ragle, Anne-Mette; Jakobsen, Henrik; Klausen, Tobias Wirenfeldt; Vinther, Anders; Sønksen, Jens

    2016-01-01

    Introduction Level 1 evidence supports the use of supervised exercise to mitigate the adverse effects of androgen deprivation therapy (ADT) in men with prostate cancer. The data, however, have been generated in controlled research settings and might not be transferable to daily clinical practice. This article describes the design of an ongoing prospective observational study to evaluate the potential benefits of exercise in daily clinical practice. Methods and analysis Men diagnosed with prostate cancer starting or already receiving ADT at our facility are invited to participate in a 12-week exercise programme implemented as the standard of care. Exclusion criteria are opioid-demanding treatment for skeletal pain, an Eastern Cooperative Oncology Group (ECOG) performance status above 2 or the inability to perform floor and machine exercises independently. The intervention consists of an initial educational session of 1½ hours followed by 12 weeks of group-based supervised training two times a week. The focus of the exercise is progressive resistance training in combination with aerobic training. Participants are measured at baseline, after 12 weeks and after 24 weeks as part of the programme. Primary endpoints of this study are changes in physical fitness evaluated by the 30 s Chair-Stand Test and Graded Cycling Test with Talk Test. Secondary endpoints include changes in quality of life, body composition and safety of exercise. Inclusion started in August 2014, with 169 participants being included by December 2015. Ethics and dissemination The study has been reviewed by the Scientific Ethical Committee of the Capital Region of Denmark (reference number H-3-2013-FSP39). The results of the study will be published in peer-reviewed international journals and will be presented at national and international conferences and symposiums. Trial registration number NCT02631681; Pre-results. PMID:27357198

  14. Expression of androgen receptor in non-muscle-invasive bladder cancer predicts the preventive effect of androgen deprivation therapy on tumor recurrence

    PubMed Central

    Miyamoto, Hiroshi; Miyoshi, Yasuhide; Ota, Junichi; Moriyama, Masatoshi; Murai, Tetsuo; Hayashi, Hiroyuki; Inayama, Yoshiaki; Ohashi, Kenichi; Yao, Masahiro; Uemura, Hiroji

    2016-01-01

    Our recent retrospective study revealed a significantly reduced risk of bladder cancer (BC) recurrence in men who received androgen deprivation therapy (ADT) for their prostate cancer. However, whether androgen receptor (AR) signals contributed to the preventive effect of ADT remained unclear because ADT could reduce serum estrogens as well. The purpose of this study is to investigate the associations between the expression of AR/estrogen receptors (ERs) and BC recurrence in patients treated with ADT. We immunohistochemically stained 72 BCs and 42 corresponding normal urothelial tissues. AR/ERα/ERβ were positive in 44(61%)/22(31%)/39(54%) tumors and 35(83%)/24(57%)/34(81%) corresponding normal urothelial tissues, respectively. There were no statistically significant correlations between AR/ERα/ERβ expression and clinicopathological features of BC. With a median follow-up of 31.3 months, 12 (43%) of 28 patients with AR-negative tumor versus 11 (23%) of 44 patients with AR-positive tumor experienced BC recurrence. Thus, patients with AR-positive tumor had a significantly lower risk of BC recurrence (P=0.031), compared with those with AR-negative tumor. Meanwhile, the expression of ERα/ERβ in tumors and that of AR/ERα/ERβ in normal urothelial tissues were not significantly correlated with BC recurrence. A multivariate analysis revealed AR positivity in tumors as an independent prognosticator (hazard ratio: 0.27; 95% confidence interval: 0.11-0.67) for BC recurrence. These results indicate that ADT prevents BC recurrence via the AR pathway, but not via the ERα/ERβ pathways. PMID:26885620

  15. Hypercholesterolemia Is Associated with a Shorter Time to Castration-Resistant Prostate Cancer in Patients Who Have Undergone Androgen Deprivation Therapy

    PubMed Central

    Jeon, Jong Chul; Park, Jaeyoung; Park, Sungchan; Moon, Kyung Hyun; Cheon, Sang Hyeon

    2016-01-01

    Purpose The goal of this study was to investigate the association between hypercholesterolemia and the time required for progression to castration-resistant prostate cancer (CRPC) in patients who have undergone androgen deprivation therapy (ADT). Materials and Methods Data from 154 patients with prostate cancer between 2005 and 2012 were reviewed retrospectively. ADT was employed as a treatment modality for these patients either due to multiple bone metastases at the time of diagnosis or due to old age in combination with other morbidities. Serum cholesterol levels and statin use were reviewed. We analyzed the factors associated with the development of CRPC after ADT treatment. The mean follow-up period was 34.8 months. Results The mean age of the patients was 71.3 years old and their mean prostate-specific antigen level was 141.8±212.6 ng/mL. Their mean cholesterol level was 175.9±37.7 mg/dL, and 14 patients (9.1%) were statin users. CRPC developed in 44 patients (28.6%), and the mean duration from ADT treatment to CRPC was 24.1 months. In a multivariate analysis, hypercholesterolemia was associated with the development of CRPC (hazard ratio [HR]=1.017, p<0.001), depending on clinical T stage (p=0.005) and the presence of bone metastasis (p<0.001). A subanalysis showed that hypercholesterolemia was associated with the development of CRPC in patients with bone metastasis (HR=1.032, p<0.001), but not in patients without bone metastasis. Conclusions Hypercholesterolemia may be associated with the development of CRPC after ADT in patients with bone metastasis. Further studies with longer follow-up periods and larger samples are needed to validate this finding. PMID:27169126

  16. Management of Hormone Deprivation Symptoms After Cancer.

    PubMed

    Faubion, Stephanie S; Loprinzi, Charles L; Ruddy, Kathryn J

    2016-08-01

    Cancer survivors often experience symptoms related to hormone deprivation, including vasomotor symptoms, genitourinary symptoms, and sexual health concerns. These symptoms can occur due to natural menopause in midlife women, or they can be brought on by oncologic therapies in younger women or men. We searched PubMed for English-language studies from January 1990 through January 2016 to identify relevant articles on the management of hormone deprivation symptoms, including vasomotor, genitourinary, and sexual symptoms in patients with cancer. The search terms used included hormone deprivation, vasomotor symptoms, hot flash, vaginal dryness, sexual dysfunction, and breast cancer. This manuscript provides a comprehensive description of data supporting the treatment of symptoms associated with hormone deprivation. PMID:27492917

  17. Dose-Escalated Radiotherapy for High-Risk Prostate Cancer: Outcomes in Modern Era With Short-Term Androgen Deprivation Therapy

    SciTech Connect

    Liauw, Stanley L.; Stadler, Walter M.; Correa, David B.S.; Weichselbaum, Ralph R.; Jani, Ashesh B.

    2010-05-01

    Purpose: Randomized data have supported the use of long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) for men with high-risk prostate cancer. The present study reviewed the outcomes of intermediate- and high-risk men treated with RT and short-term ADT. Materials and Methods: A total of 184 men with any single risk factor of prostate-specific antigen >=10 ng/mL, clinical Stage T2b or greater, or Gleason score >=7 were treated with primary external beam RT for nonmetastatic adenocarcinoma of the prostate. The median radiation dose was 74 Gy; 55% were treated with intensity-modulated RT. All patients received ADT for 1 to 6 months (median, 4), consisting of a gonadotropin-releasing hormone analog. Univariate and multivariable analyses were performed for risk factors, including T stage, Gleason score, radiation dose, and prostate-specific antigen level. Results: With a median follow-up of 51 months, the 4-year freedom from biochemical failure (FFBF) using the nadir plus 2 ng/mL definition was 83% for all patients. Clinical Stage T3 disease was the only variable tested associated with FFBF on univariate (4-year FFBF rate, 46% vs. 87% for Stage T1-T2c disease; p = .0303) and multivariable analysis (hazard ratio, 3.9; p = .0016). On a subset analysis of high-risk patients (National Comprehensive Cancer Network criteria), those with clinical Stage T3 disease (4-year FFBF rate, 46% vs. 80%; p = .0303) and a radiation dose <74 Gy (4-year FFBF rate, 64% vs. 80%) had a poorer outcome on univariate analysis. However, clinical Stage T3 disease and radiation dose were not significant on multivariable analysis, although a statistical multivariable trend was seen for both (p = .0650 and p = .0597, respectively). Conclusion: Short-term ADT and RT might be acceptable for men with intermediate- and high-risk prostate cancer, especially for clinically localized disease treated with doses of >=74 Gy.

  18. High-Dose Radiotherapy With or Without Androgen Deprivation Therapy for Intermediate-Risk Prostate Cancer: Cancer Control and Toxicity Outcomes

    SciTech Connect

    Edelman, Scott; Liauw, Stanley L.; Rossi, Peter J.; Cooper, Sherrie; Jani, Ashesh B.

    2012-08-01

    Purpose: To evaluate the impact of short-course androgen deprivation therapy (ADT) on cancer control outcomes and toxicity in intermediate-risk prostate cancer treated with dose-escalated external beam radiotherapy (high-dose radiotherapy [HDRT]). Methods and Materials: Demographic, disease, and treatment characteristics of prostate cancer patients at 2 institution consortiums were charted. Of 296 men with intermediate-risk prostate cancer (defined as {>=}T2b, prostate-specific antigen level >10 ng/mL, or Gleason score [GS] of 7, with none of the following: {>=}T3, prostate-specific antigen level >20 ng/mL, GS {>=}8, or positive nodes) treated with HDRT to a dose of 72 Gy or greater, 123 received short-course ADT and 173 did not. Univariate and multivariate analyses on biochemical failure-free survival (BFFS) (including subset analysis by disease factors) and on overall survival (OS) were performed, as were comparisons of gastrointestinal (GI) and genitourinary (GU) toxicity rates. Results: For the whole group, the median dose was 75.6 Gy; the minimum follow-up was 2 years, and the median follow-up was 47.4 months. For ADT vs. no ADT, the 5-year BFFS rate was 86% vs. 79% (p = 0.138) and the 5-year OS rate was 87% vs. 80% (p = 0.159). On multivariate analysis, percent positive cores (PPC) (p = 0.002) and GS (p = 0.008) were significantly associated with BFFS, with ADT showing a trend (p = 0.055). The impact of ADT was highest in the subsets with PPC greater than 50% (p = 0.019), GS 4+3 (p = 0.078), and number of risk factors greater than 1 (p = 0.022). Only intensity-modulated radiotherapy use (p = 0.012) and GS (p = 0.023) reached significance for OS, and there were no significant differences in GU or GI toxicity. Conclusions: Although the use of ADT with HDRT did not influence BFFS, our study suggests a benefit in patients with PPC greater than 50%, GS 4+3, or multiple risk factors. No OS benefit was shown, and ADT was not associated with additional radiotherapy

  19. Influence of Androgen Deprivation Therapy on All-Cause Mortality in Men With High-Risk Prostate Cancer and a History of Congestive Heart Failure or Myocardial Infarction

    SciTech Connect

    Nguyen, Paul L.; Chen, Ming-Hui; Beckman, Joshua A.; Beard, Clair J.; Martin, Neil E.; Choueiri, Toni K.; Hu, Jim C.; Dosoretz, Daniel E.; Moran, Brian J.; Salenius, Sharon A.; Braccioforte, Michelle H.; Kantoff, Philip W.; D'Amico, Anthony V.; Ennis, Ronald D.

    2012-03-15

    Purpose: It is unknown whether the excess risk of all-cause mortality (ACM) observed when androgen deprivation therapy (ADT) is added to radiation for men with prostate cancer and a history of congestive heart failure (CHF) or myocardial infarction (MI) also applies to those with high-risk disease. Methods and Materials: Of 14,594 men with cT1c-T3aN0M0 prostate cancer treated with brachytherapy-based radiation from 1991 through 2006, 1,378 (9.4%) with a history of CHF or MI comprised the study cohort. Of these, 22.6% received supplemental external beam radiation, and 42.9% received a median of 4 months of neoadjuvant ADT. Median age was 71.8 years. Median follow-up was 4.3 years. Cox multivariable analysis tested for an association between ADT use and ACM within risk groups, after adjusting for treatment factors, prognostic factors, and propensity score for ADT. Results: ADT was associated with significantly increased ACM (adjusted hazard ratio [AHR] = 1.76; 95% confidence interval [CI], 1.32-2.34; p = 0.0001), with 5-year estimates of 22.71% with ADT and 11.62% without ADT. The impact of ADT on ACM by risk group was as follows: high-risk AHR = 2.57; 95% CI, 1.17-5.67; p = 0.019; intermediate-risk AHR = 1.75; 95% CI, 1.13-2.73; p = 0.012; low-risk AHR = 1.52; 95% CI, 0.96-2.43; p = 0.075). Conclusions: Among patients with a history of CHF or MI treated with brachytherapy-based radiation, ADT was associated with increased all-cause mortality, even for patients with high-risk disease. Although ADT has been shown in Phase III studies to improve overall survival in high-risk disease, the small subgroup of high-risk patients with a history of CHF or MI, who represented about 9% of the patients, may be harmed by ADT.

  20. Redefining High-Risk Prostate Cancer Based on Distant Metastases and Mortality After High-Dose Radiotherapy With Androgen Deprivation Therapy

    SciTech Connect

    Tendulkar, Rahul D.; Reddy, Chandana A.; Stephans, Kevin L.; Ciezki, Jay P.; Klein, Eric A.; Mahadevan, Arul; Kupelian, Patrick A.

    2012-03-15

    Purpose: Modern outcomes of high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT) for high-risk (HR) prostate cancer are not well described. Methods and Materials: We identified 585 patients who met HR criteria by 2010 National Comprehensive Cancer Network guidelines, who were treated with EBRT consisting of {>=}74 Gy from 1996 to 2008 at Cleveland Clinic, of whom 95% received ADT. We analyzed biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM). Results: The median EBRT dose was 78 Gy, and median ADT duration was 6 months. At 10 years, the bRFS was 50.2%, the DMFS was 71.6%, and the PCSM was 14.4%. On multivariate analysis, significant predictors of bRFS were biopsy Gleason score (bGS) of 8 to 10, stage T3, and prostate-specific antigen (PSA) concentration; predictors of DMFS were bGS of 8 to 10 and stage T3; the only predictor of PCSM was bGS of 8 to 10. The duration of ADT was not predictive of any endpoint. We identified an unfavorable high-risk (UHR) group of stage T1-T2 tumors consisting of bGS of 8 with PSA of >10 ng/ml or bGS of 9 to 10 with any PSA level; the remaining clinically localized cancers comprised the favorable high-risk (FHR) group. Comparing FHR, UHR, and stage T3 groups, the DMFS rates were 81.4%, 57.8%, and 59.1% (p < 0.0001), and the PCSM rates were 7.5%, 28.4%, and 20.6% at 10 years, respectively (p = 0.006). Conclusion: A bGS of 8 to 10 is the strongest predictor of bRFS, DMFS, and PCSM after high-dose EBRT with ADT. The duration of ADT did not correlate with outcome. Future studies should account for the heterogeneity in HR prostate cancer.

  1. Decision analytic cost-effectiveness model to compare prostate cryotherapy to androgen deprivation therapy for treatment of radiation recurrent prostate cancer

    PubMed Central

    Boyd, Kathleen A; Jones, Rob J; Paul, Jim; Birrell, Fiona; Briggs, Andrew H; Leung, Hing Y

    2015-01-01

    Objective To determine the cost-effectiveness of salvage cryotherapy (SC) in men with radiation recurrent prostate cancer (RRPC). Design Cost-utility analysis using decision analytic modelling by a Markov model. Setting and methods Compared SC and androgen deprivation therapy (ADT) in a cohort of patients with RRPC (biopsy proven local recurrence, no evidence of metastatic disease). A literature review captured published data to inform the decision model, and resource use data were from the Scottish Prostate Cryotherapy Service. The model was run in monthly cycles for RRPC men, mean age of 70 years. The model was run over the patient lifetime, to assess changes in patient health states and the associated quality of life, survival and cost impacts. Results are reported in terms of the discounted incremental costs and discounted incremental quality-adjusted life years (QALYs) gained between the 2 alternative interventions. Probabilistic sensitivity analysis used a 10 000 iteration Monte Carlo simulation. Results SC has a high upfront treatment cost, but delays the ongoing monthly cost of ADT. SC is the dominant strategy over the patient lifetime; it is more effective with an incremental 0.56 QALY gain (95% CI 0.28 to 0.87), and less costly with a reduced lifetime cost of £29 719 (€37 619) (95% CI −51 985 to −9243). For a ceiling ratio of £30 000, SC has a 100% probability to be cost-effective. The cost neutral point was at 3.5 years, when the upfront cost of SC (plus any subsequent cumulative cost of side effects and ADT) equates the cumulative cost in the ADT arm. Limitations of our model may arise from its insensitivity to parameter or structural uncertainty. Conclusions The platform for SC versus ADT cost-effective analysis can be employed to evaluate other treatment modalities or strategies in RRPC. SC is the dominant strategy, costing less over a patient's lifetime with improvements in QALYs. Trial registration number This economic analysis

  2. Hormone therapy for prostate cancer

    MedlinePlus

    Androgen deprivation therapy; ADT; Androgen suppression therapy; Combined androgen blockade ... Androgens cause prostate cancer cells to grow. Hormone therapy for prostate cancer lowers the effect level of ...

  3. Population-Based Study of Cardiovascular Mortality Among Patients With Prostate Cancer Treated With Radical External Beam Radiation Therapy With and Without Adjuvant Androgen Deprivation Therapy at the British Columbia Cancer Agency

    SciTech Connect

    Kim, Julian; Vaid, Moninder; Tyldesley, Scott; Woods, Ryan; Pickles, Tom

    2011-07-01

    Purpose: There are conflicting studies of the impact of androgen deprivation therapy (ADT) on cardiovascular (CV) mortality among prostate cancer patients receiving curative intent external beam radiation therapy (EBRT). We assessed the impact of ADT on CV mortality in patients treated in British Columbia. Methods and Materials: Provincial pharmacy and radiotherapy databases were linked to the provincial cancer registry, and defined a cohort of patients treated with curative intent EBRT between 1998 and 2005. We determined the duration of ADT and the cumulative incidence of CV death. We compared death from CV disease with and without ADT, and by duration of ADT using competing risk analysis and Fine and Gray multivariant analysis. A total of 600 randomly selected patients were reviewed to determine baseline CV disease, CV risk factors, and Charlson Index. Results: Of 5,948 prostate cancer patients treated with radical intent EBRT, of whom 1,933 were treated without ADT, 674 received ADT for {<=}6 months and 3,341 received > 6 months of ADT. The cumulative CV mortality at 7 years was 2.6% (95% confidence interval [CI] 1.9-3.5%), 2.1% (95% CI = 1.2-3.5%), and 1.4 (95% CI = 1.0-2.0%) for patients with no ADT, {<=}6 months of ADT, and >6 months of ADT, respectively (Gray's p = 0.002). Baseline CV disease and risk factors were more prevalent in the no-ADT group compared with the >6-month ADT group. Conclusions: This study demonstrated a lower CV mortality rate among patients treated with longer durations of ADT than those treated without ADT. These differences likely relate to selection of patients for ADT rather than effect of ADT itself.

  4. Environmentally Deprived Children.

    ERIC Educational Resources Information Center

    Nimnicht, Glen

    This paper discusses the meaning of environmental deprivation, specifically the effects of racial, ethnic, and cultural differences on education. Objectives are also given for a Head Start and Follow Through program. A child is environmentally deprived to the extent that he has not developed his intellectual ability and a positive self-image.…

  5. Monocular Deprivation in Mice

    PubMed Central

    Li, Ya-tang; Chou, Xiao-lin; Tao, Huizhong Whit

    2016-01-01

    Monocular deprivation is an experimental technique to study the ocular dominance plasticity during critical period (Hubel and Wiesel, 1963). Generally one eye of an animal is sutured during critical period, and the sutured eye is re-opened after either less than three days (short term) or more than three days (long term). Here we describe a detailed protocol for short-term and long-term monocular deprivation in mouse (Ma et al., 2013).

  6. External-Beam Radiation Therapy and High-Dose Rate Brachytherapy Combined With Long-Term Androgen Deprivation Therapy in High and Very High Prostate Cancer: Preliminary Data on Clinical Outcome

    SciTech Connect

    Martinez-Monge, Rafael; Moreno, Marta; Ciervide, Raquel; Cambeiro, Mauricio; Perez-Gracia, Jose Luis; Gil-Bazo, Ignacio; Gaztanaga, Miren; Arbea, Leire; Pascual, Ignacio; Aristu, Javier

    2012-03-01

    Purpose: To determine the feasibility of combined long-term androgen deprivation therapy (ADT) and dose escalation with high-dose-rate (HDR) brachytherapy. Methods and Materials: Between 2001 and 2007, 200 patients with high-risk prostate cancer (32.5%) or very high-risk prostate cancer (67.5%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen of 15.2 ng/mL, a clinical stage of T2c, and a Gleason score of 7. Treatment consisted of 54 Gy of external irradiation (three-dimensional conformal radiotherapy [3DCRT]) followed by 19 Gy of HDR brachytherapy in four twice-daily treatments. ADT started 0-3 months before 3DCRT and continued for 2 years. Results: One hundred and ninety patients (95%) received 2 years of ADT. After a median follow-up of 3.7 years (range, 2-9), late Grade {>=}2 urinary toxicity was observed in 18% of the patients and Grade {>=}3 was observed in 5%. Prior transurethral resection of the prostate (p = 0.013) and bladder D{sub 50} {>=}1.19 Gy (p = 0.014) were associated with increased Grade {>=}2 urinary complications; age {>=}70 (p = 0.05) was associated with Grade {>=}3 urinary complications. Late Grade {>=}2 gastrointestinal toxicity was observed in 9% of the patients and Grade {>=}3 in 1.5%. CTV size {>=}35.8 cc (p = 0.007) and D{sub 100} {>=}3.05 Gy (p = 0.01) were significant for increased Grade {>=}2 complications. The 5-year and 9-year biochemical relapse-free survival (nadir + 2) rates were 85.1% and 75.7%, respectively. Patients with Gleason score of 7-10 had a decreased biochemical relapse-free survival (p = 0.007). Conclusions: Intermediate-term results at the 5-year time point indicate a favorable outcome without an increase in the rate of late complications.

  7. Was cultural deprivation in fact sensory deprivation? Deprivation, retardation and intervention in the USA.

    PubMed

    Raz, Mical

    2011-01-01

    In the 1950s, the term "deprivation" entered American psychiatric discourse. This article examines how the concept of deprivation permeated the field of mental retardation, and became an accepted theory of etiology. It focuses on sensory deprivation and cultural deprivation, and analyzes the interventions developed, based on these theories. It argues that the controversial theory of cultural deprivation derived its scientific legitimization from the theory of sensory deprivation, and was a highly politicized concept that took part in the nature-nurture debate. PMID:21488428

  8. Deprivation and Communication.

    ERIC Educational Resources Information Center

    Cloke, Daphne

    1983-01-01

    A case study of a pair of extremely deprived twin boys focuses on their verbal communication. Talkativeness alone was not regarded as a measure of intelligence, but attention was paid to the less talkative twin's greater use of imaginative speech. Speculations are made on the evolutionary role of creative speech. (IS)

  9. Androgen deprivation treatment of sexual behavior.

    PubMed

    Houts, Frederick W; Taller, Inna; Tucker, Douglas E; Berlin, Fred S

    2011-01-01

    Gonadotropin-releasing hormone agonists are underutilized in patients seeking diminution of problematic sexual drives. This chapter reviews the literature on surgical castration of sex offenders, anti-androgen use and the rationale for providing androgen deprivation therapy, rather than selective serotonin reuptake inhibitors or more conservative interventions, for patients with paraphilias and excessive sexual drive. Discussions of informed consent, side effects, contraindications and case examples are provided. PMID:22005210

  10. Long-term androgen deprivation therapy improves survival in prostate cancer patients presenting with prostate-specific antigen levels >20 ng/mL

    SciTech Connect

    Berthelet, Eric . E-mail: eberthel@bccancer.bc.ca; Pickles, Tom; Lee, Kenny Won Jae; Liu, Mitchell; Truong, Pauline T.

    2005-11-01

    Purpose: To assess the benefit of androgen deprivation (AD) and its optimal duration in patients with prostate cancer treated with external beam radiotherapy, who present with prostate-specific antigen levels >20 ng/mL. Methods and Materials: A total of 307 patients treated with external beam radiotherapy, AD, and presenting with a PSA level >20 ng/mL were identified from the Prostate Cancer Outcomes Initiative database of the British Columbia Cancer Agency. Androgen deprivation was defined as short term (ST-AD, <12 months) or long term (LT-AD, {>=}12 months). The endpoints analyzed were biochemical control (no evidence of disease) (bNED), overall survival, and cause-specific survival. Statistical analysis was conducted with Kaplan-Meier estimates, log-rank tests, and multivariate analyses with logistic and Cox regression models. Results: There were 151 patients in the ST-AD group and 156 in the LT-AD group. The distributions of Gleason score and stage were comparable in the two cohorts. Median follow-up times were 48 months for patients treated with ST-AD and 45 months for patients treated with LT-AD. The median durations of AD were 6 and 25.6 months for the ST-AD and LT-AD groups, respectively. The bNED rate was 37% for the ST-AD group and 62.5% for the LT-AD group (p < 0.0001). The 5-year overall survival rate was 75% in the ST-AD group vs. 87.5% for the LT-AD group (p = 0.0091). The 5-year cause-specific survival rate was 82% for the ST-AD group vs. 94% for the LT-AD group (p = 0.0072). Conclusions: Several randomized trials have demonstrated the benefit of LT-AD in high-risk patients with prostate cancer. In some reports, the survival advantage seems to be restricted to patients with high Gleason score. The present analysis supports the hypothesis that LT-AD improves bNED and survival rates in patients presenting with a PSA level >20, irrespective of Gleason score or T stage.

  11. Unihemispheric sleep deprivation in bottlenose dolphins.

    PubMed

    Oleksenko; Mukhametov; Polyakova; Supin; Kovalzon

    1992-03-01

    Unihemispheric and bihemispheric sleep deprivation were performed in bottlenose dolphins. One brain hemisphere was capable of being deprived of delta (0.5-3.0 Hz) sleep in the former condition. Here, an increase in sleep pressure was observed during sleep deprivation in the deprived hemisphere. In the recovery sleep, following unihemispheric sleep deprivation, there was a rebound of delta sleep only in the deprived hemisphere. Following bihemispheric sleep deprivation the animals exhibited an increase in delta sleep in both hemispheres. PMID:10607024

  12. Modulation of cell cycle and gene expression in pancreatic tumor cell lines by methionine deprivation (methionine stress): implications to the therapy of pancreatic adenocarcinoma.

    PubMed

    Kokkinakis, Demetrius M; Liu, Xiaoyan; Neuner, Russell D

    2005-09-01

    The effect of methionine deprivation (methionine stress) on the proliferation, survival, resistance to chemotherapy, and regulation of gene and protein expression in pancreatic tumor lines is examined. Methionine stress prevents successful mitosis and promotes cell cycle arrest and accumulation of cells with multiple micronuclei with decondensed chromatin. Inhibition of mitosis correlates with CDK1 down-regulation and/or inhibition of its function by Tyr(15) phosphorylation or Thr(161) dephosphorylation. Inhibition of cell cycle progression correlates with loss of hyperphosphorylated Rb and up-regulation of p21 via p53 and/or transforming growth factor-beta (TGF-beta) activation depending on p53 status. Although methionine stress-induced toxicity is not solely dependent on p53, the gain in p21 and loss in CDK1 transcription are more enhanced in wild-type p53 tumors. Up-regulation of SMAD7, a TGF-beta signaling inhibitor, suggests that SMAD7 does not restrict the TGF-beta-mediated induction of p21, although it may prevent up-regulation of p27. cDNA oligoarray analysis indicated a pleiotropic response to methionine stress. Cell cycle and mitotic arrest is in agreement with up-regulation of NF2, ETS2, CLU, GADD45alpha, GADD45beta, and GADD45gamma and down-regulation of AURKB, TOP2A, CCNA, CCNB, PRC1, BUB1, NuSAP, IFI16, and BRCA1. Down-regulation of AREG, AGTR1, M-CSF, and EGF, IGF, and VEGF receptors and up-regulation of GNA11 and IGFBP4 signify loss of growth factor support. PIN1, FEN1, and cABL up-regulation and LMNB1, AREG, RhoB, CCNG, TYMS, F3, and MGMT down-regulation suggest that methionine stress sensitizes the tumor cells to DNA-alkylating drugs, 5-fluorouracil, and radiation. Increased sensitivity of pancreatic tumor cell lines to temozolomide is shown under methionine stress conditions and is attributed in part to diminished O(6)-methylguanine-DNA methyltransferase and possibly to inhibition of the cell cycle progression. PMID:16170025

  13. Retrospective Evaluation Reveals That Long-term Androgen Deprivation Therapy Improves Cause-Specific and Overall Survival in the Setting of Dose-Escalated Radiation for High-Risk Prostate Cancer

    SciTech Connect

    Feng, Felix Y.; Blas, Kevin; Olson, Karin; Stenmark, Matthew; Sandler, Howard; Hamstra, Daniel A.

    2013-05-01

    Purpose: To evaluate the role of androgen deprivation therapy (ADT) and duration for high-risk prostate cancer patients treated with dose-escalated radiation therapy (RT). Methods and Materials: A retrospective analysis of high-risk prostate cancer patients treated with dose-escalated RT (minimum 75 Gy) with or without ADT was performed. The relationship between ADT use and duration with biochemical failure (BF), metastatic failure (MF), prostate cancer-specific mortality (PCSM), non-prostate cancer death (NPCD), and overall survival (OS) was assessed as a function of pretreatment characteristics, comorbid medical illness, and treatment using Fine and Gray's cumulative incidence methodology. Results: The median follow-up time was 64 months. In men with National Comprehensive Cancer Network defined high-risk prostate cancer treated with dose-escalated RT, on univariate analysis, both metastasis (P<.0001; hazard ratio 0.34; 95% confidence interval 0.18-0.67; cumulative incidence at 60 months 13% vs 35%) and PCSM (P=.015; hazard ratio 0.41; 95% confidence interval 0.2-1.0; cumulative incidence at 60 months 6% vs 11%) were improved with the use of ADT. On multivariate analysis for all high-risk patients, Gleason score was the strongest negative prognostic factor, and long-term ADT (LTAD) improved MF (P=.002), PCSM (P=.034), and OS (P=.001). In men with prostate cancer and Gleason scores 8 to 10, on multivariate analysis after adjustment for other risk features, there was a duration-dependent improvement in BF, metastasis, PCSM, and OS, all favoring LTAD in comparison with STAD or RT alone. Conclusion: For men with high-risk prostate cancer treated with dose-escalated EBRT, this retrospective study suggests that the combination of LTAD and RT provided a significant improvement in clinical outcome, which was especially true for those with Gleason scores of 8 to 10.

  14. Consequences of sleep deprivation.

    PubMed

    Orzeł-Gryglewska, Jolanta

    2010-01-01

    This paper presents the history of research and the results of recent studies on the effects of sleep deprivation in animals and humans. Humans can bear several days of continuous sleeplessness, experiencing deterioration in wellbeing and effectiveness; however, also a shorter reduction in the sleep time may lead to deteriorated functioning. Sleeplessness accounts for impaired perception, difficulties in keeping concentration, vision disturbances, slower reactions, as well as the appearance of microepisodes of sleep during wakefulness which lead to lower capabilities and efficiency of task performance and to increased number of errors. Sleep deprivation results in poor memorizing, schematic thinking, which yields wrong decisions, and emotional disturbances such as deteriorated interpersonal responses and increased aggressiveness. The symptoms are accompanied by brain tissue hypometabolism, particularly in the thalamus, prefrontal, frontal and occipital cortex and motor speech centres. Sleep deficiency intensifies muscle tonus and coexisting tremor, speech performance becomes monotonous and unclear, and sensitivity to pain is higher. Sleeplessness also relates to the changes in the immune response and the pattern of hormonal secretion, of the growth hormone in particular. The risk of obesity, diabetes and cardiovascular disease increases. The impairment of performance which is caused by 20-25 hours of sleeplessness is comparable to that after ethanol intoxication at the level of 0.10% blood alcohol concentration. The consequences of chronic sleep reduction or a shallow sleep repeated for several days tend to accumulate and resemble the effects of acute sleep deprivation lasting several dozen hours. At work, such effects hinder proper performance of many essential tasks and in extreme situations (machine operation or vehicle driving), sleep loss may be hazardous to the worker and his/her environment. PMID:20442067

  15. 68Ga-Labeled Anti-Prostate-Specific Membrane Antigen Peptide as Marker for Androgen Deprivation Therapy Response in Prostate Cancer.

    PubMed

    Schlenkhoff, Carl Diedrich; Gaertner, Florian; Essler, Markus; Hauser, Stefan; Ahmadzadehfar, Hojjat

    2016-05-01

    Prostate cancer was diagnosed in a 71-year-old man with an elevated prostate-specific antigen. The CT of the abdomen showed multiple para-aortal lymph nodes, and thus, a Ga anti-prostate-specific membrane antigen (PSMA-11) PET/CT was initiated, which showed, aside from the prostate cancer and multiple iliacal and para-aortal lymph node metastases, an increased tracer uptake in a lymph node left cervical. According to this advanced disease, a palliative therapy with GnRH agonist was initiated. A second PSMA-11 PET/CT was performed 4 months later, which showed a very good response; thus, additional radiation of the pelvis and the draining lymphatic system was performed. PMID:26859213

  16. Response deprivation, reinforcement, and economics

    PubMed Central

    Allison, James

    1993-01-01

    Reinforcement of an instrumental response results not from a special kind of response consequence known as a reinforcer, but from a special kind of schedule known as a response-deprivation schedule. Under the requirements of a response-deprivation schedule, the baseline rate of the instrumental response permits less than the baseline rate of the contingent response. Because reinforcement occurs only if the schedule deprives the organism of the contingent response, reinforcement cannot result from any intrinsic property of the contingent response or any property relative to the instrumental response. Two typical effects of response-deprivation schedules—facilitation of the instrumental response and suppression of the contingent response—are discussed in terms of economic concepts and models of instrumental performance. It is suggested that response deprivation makes the contingent response function as an economic good, the instrumental response as currency. PMID:16812695

  17. Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT) and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis

    PubMed Central

    Botrel, Tobias Engel Ayer; Clark, Otávio; Lima Pompeo, Antônio Carlos; Horta Bretas, Francisco Flávio; Sadi, Marcus Vinicius; Ferreira, Ubirajara; Borges dos Reis, Rodolfo

    2016-01-01

    Objective Prostate cancer is the most common nonskin cancer and second most common cause of cancer mortality in older men in the United States (USA) and Western Europe. Androgen-deprivation therapy alone (ADT) remains the first line of treatment in most cases, for metastatic disease. We performed a systematic review and meta-analysis of all randomized controlled trials (RCT) that compared the efficacy and adverse events profile of a chemohormonal therapy (ADT ± docetaxel) for metastatic hormone-naive prostate cancer (mHNPC). Methods Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoint was overall survival. Data extracted from the studies were combined by using the hazard ratio (HR) or risk ratio (RR) with their corresponding 95% confidence intervals (95% CI). Results The final analysis included 3 trials comprising 2,264 patients (mHNPC). Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001), and no heterogeneity (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%). The biochemical progression-free survival (bPFS) also was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p<0.00001), also with no heterogeneity noted (Chi2 = 0.48; df = 2 [p = 0.79]; I2 = 0%). Finally, the combination of ADT with docetaxel showed a superior overall survival (OS) compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001), with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%). A random-effects model analysis was performed, and the results remained favorable to the use of ADT plus docetaxel (HR = 0.73; 95% CI: 0.60 to 0.89; p = 0.002). In the final combined analysis of the high-volume disease patients, the use of the combination therapy also favored an increased overall survival (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003). Regarding adverse events and severe toxicity (grade ≥3), the group

  18. [Delusion and sleep deprivation].

    PubMed

    Devillières, P; Opitz, M; Clervoy, P; Stephany, J

    1996-01-01

    In this article, the authors report two observations of short delusion that occurred after taking Guronsan--a psychostimulant commercialized in France--for a few days, with the intention of maintaining a total deprivation of sleep for three days in both cases. The ensuing clinical picture included a state of depersonalization, a loss of the sense of reality, illusions and even visual hallucinations as well as a delirious feeling of persecution. These disorders altered with the state of vigilance and the patients remembered them clearly. The authors discussed the etiopathogenic role of this psychotrope, as its components--acid ascorbic, glucuronamide and caffein--are not mentioned in literature as causing factors of a psychotic state. Then they compared this psychotrope with other molecules: amphetamines in particular may start a delirium of persecution, but normally they just reveal an underlying psychotic structure, which doesn't seem to be the case here, where the two young adults were only found a little immature. Chloroquine has sometimes been incriminated for disorders similar to those mentioned above, with a difference lying in a greater stability in the duration of these disorders that would persist several days after the end of the treatment. The clinical picture of the two cases was more labile and sedation was complete as soon as the absorption of the psychotrope was interrupted and sleep was restored at the same time. That is why the authors emphasize the importance of the deprivation of sleep as a causing factor of those delusion disorders which have particularly been observed in the case of solitary navigators. The psychiatrist dealing with emergencies shouldn't overlook this clinical and etiological possibility, all the less so as the treatment is simple and the resort to neuroleptics unnecessary. PMID:8767052

  19. Sleep Deprivation and Advice Taking.

    PubMed

    Häusser, Jan Alexander; Leder, Johannes; Ketturat, Charlene; Dresler, Martin; Faber, Nadira Sophie

    2016-01-01

    Judgements and decisions in many political, economic or medical contexts are often made while sleep deprived. Furthermore, in such contexts individuals are required to integrate information provided by - more or less qualified - advisors. We asked if sleep deprivation affects advice taking. We conducted a 2 (sleep deprivation: yes vs. no) ×2 (competency of advisor: medium vs. high) experimental study to examine the effects of sleep deprivation on advice taking in an estimation task. We compared participants with one night of total sleep deprivation to participants with a night of regular sleep. Competency of advisor was manipulated within subjects. We found that sleep deprived participants show increased advice taking. An interaction of condition and competency of advisor and further post-hoc analyses revealed that this effect was more pronounced for the medium competency advisor compared to the high competency advisor. Furthermore, sleep deprived participants benefited more from an advisor of high competency in terms of stronger improvement in judgmental accuracy than well-rested participants. PMID:27109507

  20. Sleep Deprivation and Advice Taking

    PubMed Central

    Häusser, Jan Alexander; Leder, Johannes; Ketturat, Charlene; Dresler, Martin; Faber, Nadira Sophie

    2016-01-01

    Judgements and decisions in many political, economic or medical contexts are often made while sleep deprived. Furthermore, in such contexts individuals are required to integrate information provided by – more or less qualified – advisors. We asked if sleep deprivation affects advice taking. We conducted a 2 (sleep deprivation: yes vs. no) ×2 (competency of advisor: medium vs. high) experimental study to examine the effects of sleep deprivation on advice taking in an estimation task. We compared participants with one night of total sleep deprivation to participants with a night of regular sleep. Competency of advisor was manipulated within subjects. We found that sleep deprived participants show increased advice taking. An interaction of condition and competency of advisor and further post-hoc analyses revealed that this effect was more pronounced for the medium competency advisor compared to the high competency advisor. Furthermore, sleep deprived participants benefited more from an advisor of high competency in terms of stronger improvement in judgmental accuracy than well-rested participants. PMID:27109507

  1. Prostate-specific antigen (Pasa) bounce and other fluctuations: Which biochemical relapse definition is least prone to PSA false calls? An analysis of 2030 men treated for prostate cancer with external beam or brachytherapy with or without adjuvant androgen deprivation therapy

    SciTech Connect

    Pickles, Tom . E-mail: tpickles@bccancer.bc.ca

    2006-04-01

    Purpose: To determine the false call (FC) rate for prostate-specific antigen (PSA) relapse according to nine different PSA relapse definitions after a PSA fluctuation (bounce) has occurred after external beam radiation therapy (EBRT) or brachytherapy, with or without adjuvant androgen deprivation therapy. Methods and Materials: An analysis of a prospective database of 2030 patients was conducted. Prostate-specific antigen relapse was scored according to the American Society for Therapeutic Radiology and Oncology (ASTRO), Vancouver, threshold + n, and nadir + n definitions for the complete data set and then compared against a truncated data set, with data subsequent to the height of the bounce deleted. The FC rate was calculated for each definition. Results: The bounce rate, with this very liberal definition of bounce, was 58% with EBRT and 84% with brachytherapy. The FC rate was lowest with nadir + 2 and + 3 definitions (2.2% and 1.6%, respectively) and greatest with low-threshold and ASTRO definitions (32% and 18%, respectively). The ASTRO definition was particularly susceptible to FC when androgen deprivation therapy was used with radiation (24%). Discussion: New definitions of biochemical non-evidence of disease that are more robust than the ASTRO definition have been identified. Those with the least FC rates are the nadir + 2 and nadir + 3 definitions, both of which are being considered to replace the ASTRO definition by the 2005 meeting of the Radiation Therapy Oncology Group-ASTRO consensus panel.

  2. Identifying a deprivation of liberty.

    PubMed

    Griffith, Richard

    2016-01-01

    The UK Supreme Court's judgment in Cheshire West and Chester Council v P [2014] fundamentally changed the approach to determining if a person who lacked capacity was deprived of their liberty by the State. The Supreme Court further held that a deprivation of liberty could occur in any care setting including a person's own home. In this article, Richard Griffith discusses the approach district nurses should adopt when determining whether a patient being cared for at home is deprived of his/her liberty. PMID:26692137

  3. Effects of Prolonged Deprivation on Learned Helplessness.

    ERIC Educational Resources Information Center

    Mal, Suraj; And Others

    1990-01-01

    Investigated influence of prolonged deprivation on responses to uncontrollable outcome among 104 Indian students in the tenth grade. Finds high-deprived and female students displayed greater helplessness than did their low-deprived and male counterparts. Females and high-deprives students attributed uncontrollable outcome more to internal, stable,…

  4. Neurobiological Consequences of Sleep Deprivation

    PubMed Central

    Alkadhi, Karim; Zagaar, Munder; Alhaider, Ibrahim; Salim, Samina; Aleisa, Abdulaziz

    2013-01-01

    Although the physiological function of sleep is not completely understood, it is well documented that it contributes significantly to the process of learning and memory. Ample evidence suggests that adequate sleep is essential for fostering connections among neuronal networks for memory consolidation in the hippocampus. Sleep deprivation studies are extremely valuable in understanding why we sleep and what are the consequences of sleep loss. Experimental sleep deprivation in animals allows us to gain insight into the mechanism of sleep at levels not possible to study in human subjects. Many useful approaches have been utilized to evaluate the effect of sleep loss on cognitive function, each with relative advantages and disadvantages. In this review we discuss sleep and the detrimental effects of sleep deprivation mostly in experimental animals. The negative effects of sleep deprivation on various aspects of brain function including learning and memory, synaptic plasticity and the state of cognition-related signaling molecules are discussed. PMID:24179461

  5. Microarchitecture and Peripheral BMD are Impaired in Postmenopausal White Women With Fracture Independently of Total Hip T-Score: An International Multicenter Study.

    PubMed

    Boutroy, Stephanie; Khosla, Sundeep; Sornay-Rendu, Elisabeth; Zanchetta, Maria Belen; McMahon, Donald J; Zhang, Chiyuan A; Chapurlat, Roland D; Zanchetta, Jose; Stein, Emily M; Bogado, Cesar; Majumdar, Sharmila; Burghardt, Andrew J; Shane, Elizabeth

    2016-06-01

    Because single-center studies have reported conflicting associations between microarchitecture and fracture prevalence, we included high-resolution peripheral quantitative computed tomography (HR-pQCT) data from five centers worldwide into a large multicenter analysis of postmenopausal women with and without fracture. Volumetric BMD (vBMD) and microarchitecture were assessed at the distal radius and tibia in 1379 white postmenopausal women (age 67 ± 8 years); 470 (34%) had at least one fracture including 349 with a major fragility fracture. Age, height, weight, and total hip T-score differed across centers and were employed as covariates in analyses. Women with fracture had higher BMI, were older, and had lower total hip T-score, but lumbar spine T-score was similar between groups. At the radius, total and trabecular vBMD and cortical thickness were significantly lower in fractured women in three out of five centers, and trabecular number in two centers. Similar results were found at the tibia. When data from five centers were combined, however, women with fracture had significantly lower total, trabecular, and cortical vBMD (2% to 7%), lower trabecular number (4% to 5%), and thinner cortices (5% to 6%) than women without fracture after adjustment for covariates. Results were similar at the radius and tibia. Similar results were observed with analysis restricted to major fragility fracture, vertebral and hip fractures, and peripheral fracture (at the radius). When focusing on osteopenic women, each SD decrease of total and trabecular vBMD was associated with a significantly increased risk of major fragility fracture (OR = 1.55 to 1.88, p < 0.01) after adjustment for covariates. Moreover, trabecular architecture modestly improved fracture discrimination beyond peripheral total vBMD. In conclusion, we observed differences by center in the magnitude of fracture/nonfracture differences at both the distal radius and tibia. However, when data were pooled across

  6. Long-Term Follow-Up of a Prospective Trial of Trimodality Therapy of Weekly Paclitaxel, Radiation, and Androgen Deprivation in High-Risk Prostate Cancer With or Without Prior Prostatectomy

    SciTech Connect

    Hussain, Arif; Wu, Yin; Mirmiran, Alireza; DiBiase, Steven; Goloubeva, Olga; Bridges, Benjamin; Mannuel, Heather; Engstrom, Christine; Dawson, Nancy; Amin, Pradip; Kwok, Young

    2012-01-01

    Purpose: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). Methods and Materials: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) {>=}0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20-150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m{sup 2}/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). Results: Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8-82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. Conclusions: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m{sup 2}/week in RP patients and 60 mg/m{sup 2}/week in LAPC patients is

  7. Progressive Improvement of T-Scores in Men with Osteoporosis and Subnormal Serum Testosterone Levels upon Treatment with Testosterone over Six Years.

    PubMed

    Haider, Ahmad; Meergans, Ulrich; Traish, Abdulmaged; Saad, Farid; Doros, Gheorghe; Lips, Paul; Gooren, Louis

    2014-01-01

    Testosterone deficiency leads to bone loss and testosterone treatment has a beneficial effect. This study investigated the effects of normalizing serum testosterone on bone mineral density in 45 men with osteoporosis, diagnosed with testosterone deficiency (serum testosterone levels <12.1 nmol/L, T-scores: (mean ± SD) -3.12 ± 0.45, minimum: -4.10, and maximum: -2.60). In a cumulative, prospective, registry study of hypogonadal men (mean age: 53 ± 7 years) they received parenteral testosterone undecanoate of 1000 mg/12 weeks for up to six years. After one year 44 men were included in the registry, after two years 36 men, after three years 32 men, after four years 25 men, after five years 10 men and after six years 4 men. The declining numbers do not reflect drop-out rates but are a result of the registry design. Over the 6 year period there was a significant and progressive improvement of the T-scores in these men. Normalizing of serum testosterone leads to an improvement of bone mineral density and this improvement was progressive with the time period of testosterone administration. In this study of 6-years many men with testosterone deficiency suffered from classical diagnoses (Klinefelter's syndrome and testicular pathology) hitherto undiagnosed. PMID:24688541

  8. SOCIODEMOGRAPHIC DOAMINS OF DEPRIVATION AND PRETERM BIRTH

    EPA Science Inventory

    Background. Neighborhood-level deprivation has long been associated with adverse outcomes, including preterm birth (PTB), as observed in the authors' previous work using a composite deprivation index. Area disadvantage is multifaceted comprising income, employment, education and...

  9. Deprivation in Education. Final Report

    ERIC Educational Resources Information Center

    Cook, Rose; Rutt, Simon; Sims, David

    2014-01-01

    The interaction between deprivation and education is a critical relationship with profound implications for a country's economic prosperity and the social mobility of its citizens. This is highlighted by the Welsh Government which states that: "A good education is critical to better life chances and a commitment to achieving this has been an…

  10. Materialistic Cues Boosts Personal Relative Deprivation

    PubMed Central

    Zhang, Hong; Zhang, Wen

    2016-01-01

    Three studies investigated whether exposure to materialistic cues would increase perceptions of personal relative deprivation and related emotional reactions. In Study 1, individuals who were surveyed in front of a luxury store reported higher levels of personal relative deprivation than those surveyed in front of an ordinary building. In Study 2, participants who viewed pictures of luxurious goods experienced greater personal relative deprivation than those viewed pictures of neutral scenes. Study 3 replicated the results from Study 2, with a larger sample size and a more refined assessment of relative deprivation. Implications of these findings for future studies on relative deprivation and materialism are discussed. PMID:27574515

  11. Sleep deprivation and false confessions.

    PubMed

    Frenda, Steven J; Berkowitz, Shari R; Loftus, Elizabeth F; Fenn, Kimberly M

    2016-02-23

    False confession is a major contributor to the problem of wrongful convictions in the United States. Here, we provide direct evidence linking sleep deprivation and false confessions. In a procedure adapted from Kassin and Kiechel [(1996) Psychol Sci 7(3):125-128], participants completed computer tasks across multiple sessions and repeatedly received warnings that pressing the "Escape" key on their keyboard would cause the loss of study data. In their final session, participants either slept all night in laboratory bedrooms or remained awake all night. In the morning, all participants were asked to sign a statement, which summarized their activities in the laboratory and falsely alleged that they pressed the Escape key during an earlier session. After a single request, the odds of signing were 4.5 times higher for the sleep-deprived participants than for the rested participants. These findings have important implications and highlight the need for further research on factors affecting true and false confessions. PMID:26858426

  12. Child pedestrian casualties and deprivation.

    PubMed

    Green, James; Muir, Helen; Maher, Mike

    2011-05-01

    The existence of an association between child pedestrian accidents and socio-economic deprivation in Great Britain is well established. The factors driving this association are complex and difficult to isolate. This study uses accident prediction models to investigate the links between child pedestrian casualties and a range of environmental and socio-economic factors commonly linked to deprived areas and people. Separate models are constructed relating to the areas in which the children become casualties, and the areas in which the children reside. Significant socio-economic factors include: single-parenthood, reliance on income support, and crime; and environmental factors include domestic garden area, junction density and pedestrian and vehicular flow density. The study found that factors pertaining to the local environment were more prevalent in the models considering accident locations, whilst socio-economic factors were of greater influence in the residency model. PMID:21376859

  13. Occlusion for stimulus deprivation amblyopia

    PubMed Central

    Antonio-Santos, Aileen; Vedula, Satyanarayana S; Hatt, Sarah R; Powell, Christine

    2014-01-01

    Background Stimulus deprivation amblyopia (SDA) develops due to an obstruction to the passage of light secondary to a condition such as cataract. The obstruction prevents formation of a clear image on the retina. SDA can be resistant to treatment, leading to poor visual prognosis. SDA probably constitutes less than 3% of all amblyopia cases, although precise estimates of prevalence are unknown. In developed countries, most patients present under the age of one year; in less developed parts of the world patients are likely to be older at the time of presentation. The mainstay of treatment is removal of the cataract and then occlusion of the better-seeing eye, but regimens vary, can be difficult to execute, and traditionally are believed to lead to disappointing results. Objectives Our objective was to evaluate the effectiveness of occlusion therapy for SDA in an attempt to establish realistic treatment outcomes. Where data were available, we also planned to examine evidence of any dose response effect and to assess the effect of the duration, severity, and causative factor on the size and direction of the treatment effect. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2013), EMBASE (January 1980 to October 2013), the Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2013), PubMed (January 1946 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 October 2013. Selection criteria We planned

  14. Sleep deprivation and false confessions

    PubMed Central

    Frenda, Steven J.; Berkowitz, Shari R.; Loftus, Elizabeth F.; Fenn, Kimberly M.

    2016-01-01

    False confession is a major contributor to the problem of wrongful convictions in the United States. Here, we provide direct evidence linking sleep deprivation and false confessions. In a procedure adapted from Kassin and Kiechel [(1996) Psychol Sci 7(3):125–128], participants completed computer tasks across multiple sessions and repeatedly received warnings that pressing the “Escape” key on their keyboard would cause the loss of study data. In their final session, participants either slept all night in laboratory bedrooms or remained awake all night. In the morning, all participants were asked to sign a statement, which summarized their activities in the laboratory and falsely alleged that they pressed the Escape key during an earlier session. After a single request, the odds of signing were 4.5 times higher for the sleep-deprived participants than for the rested participants. These findings have important implications and highlight the need for further research on factors affecting true and false confessions. PMID:26858426

  15. Deprivation Index for Small Areas in Spain

    ERIC Educational Resources Information Center

    Sanchez-Cantalejo, Carmen; Ocana-Riola, Ricardo; Fernandez-Ajuria, Alberto

    2008-01-01

    The term deprivation is often used to refer to economic or social shortages in a given geographical area. This concept of deprivation has been identified for years using simple indicators such as income level, education and social class. One of the advantages of using simple indicators is the availability of data, since they come directly from…

  16. Resident Performance and Sleep Deprivation: A Review.

    ERIC Educational Resources Information Center

    Asken, Michael J.; Raham, David C.

    1983-01-01

    A review of the literature on resident performance and sleep deprivation suggests that current research is sparse and inconclusive, and existing research suggests potentially severe negative effects. It is proposed that justifications for sleep-depriving night call schedules remain untested, and their use as part of residency training should be…

  17. Sleep deprivation suppresses aggression in Drosophila

    PubMed Central

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

  18. Sleep deprivation suppresses aggression in Drosophila.

    PubMed

    Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

    2015-01-01

    Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. PMID:26216041

  19. Positive association of female overactive bladder symptoms and estrogen deprivation

    PubMed Central

    Cheng, Chen-Li; Li, Jian-Ri; Lin, Ching-Heng; de Groat, William C.

    2016-01-01

    Abstract Objective: Estrogen is considered to be a unique hormone in females that has an impact on voiding function. Animal models and clinical epidemiologic studies showed high correlation between estrogen deficiency and female overactive bladder (OAB) symptoms. We designed a population-based cohort study from a national health database to assess the association of estrogen deprivation therapy and female OAB. Materials and methods: This study examined the records of 16,128 patients ranging in age from 18 to 40 that were included in the Taiwan National Health Insurance Research Database (NHIRD) in the years between 2001 and 2010. Of these, 1008 had breast cancer with hormone therapy only and the other 15,120 controls did not have breast cancer or hormone therapy. All patients with neurologic diseases and those with pre-existing OAB identified by information in the NHIRD database were excluded. OAB was defined by medications prescribed for at least 1 month. Risk of new onset OAB in the breast cancer and nonbreast cancer groups was estimated. Fourteen patients (1.4%) experienced OAB in the breast cancer group. Overall, breast cancer with estrogen deprivation therapy increased the risk of OAB by 14.37-fold (adjusted hazard ratio, 95% confidence interval 7.06–29.27). Subgroup analysis showed that in the older age breast cancer group (36–40), a lower Charlson comorbidity index (CCI) score and antidepressant medication use for at least 30 days had an impact on the increase of OAB risk. After adjustment of variables, the higher CCI and the use of antipsychotic drugs increased risk of OAB 3.45-fold and 7.45-fold, respectively. The Kaplan–Meier analysis of OAB-free survival in the breast cancer group showed a significant time-dependent increase in incidence of OAB. Conclusion: Estrogen deprivation in young patients with breast cancer increased the risk of OAB. The OAB development rate was steady and fast in the beginning 3 years after estrogen deprivation. This result

  20. [Smoking cessation and social deprivation].

    PubMed

    Merson, F; Perriot, J; Underner, M; Peiffer, G; Fieulaine, N

    2014-12-01

    Smoking is a major of public health policy issue; one in two lifelong smokers will die from a disease related to tobacco use. In France, smoking is responsible for more than 70,000 deaths every year. The benefits linked to stopping smoking include reduced mortality and morbidity related to the use of tobacco. Recent data show an increase in the prevalence of smoking in the lowest socioeconomic population. Tobacco control needs a better understanding of the determinants of smoking in this population, which are also factors in the failure of cessation attempts. Based on international literature, this review specifies the educational and socioeconomic factors involved in tobacco smoking and in the result of an attempt to quit. Its aim is to propose ways to improve the management of smoking cessation in a socially deprived population. PMID:25496789

  1. Sleep deprivation: consequences for students.

    PubMed

    Marhefka, Julie King

    2011-09-01

    During the adolescent years, a delayed pattern of the sleep-wake cycle occurs. Many parents and health care providers are not aware that once established, these poor sleep habits can continue into adulthood. Early school hours start a pattern of sleep loss that begins a cycle of daytime sleepiness, which may affect mood, behavior, and increase risk for accidents or injury. These sleep-deprived habits established in adolescence can often lead to problems during college years. Sleep hygiene can be initiated to help break the cycle, along with education and implementation of a strict regimen. Monitoring all adolescents and college-aged students for sleep insufficiency is imperative to improve both academic and emotional well-being. PMID:21846079

  2. Immediate error correction process following sleep deprivation.

    PubMed

    Hsieh, Shulan; Cheng, I-Chen; Tsai, Ling-Ling

    2007-06-01

    Previous studies have suggested that one night of sleep deprivation decreases frontal lobe metabolic activity, particularly in the anterior cingulated cortex (ACC), resulting in decreased performance in various executive function tasks. This study thus attempted to address whether sleep deprivation impaired the executive function of error detection and error correction. Sixteen young healthy college students (seven women, nine men, with ages ranging from 18 to 23 years) participated in this study. Participants performed a modified letter flanker task and were instructed to make immediate error corrections on detecting performance errors. Event-related potentials (ERPs) during the flanker task were obtained using a within-subject, repeated-measure design. The error negativity or error-related negativity (Ne/ERN) and the error positivity (Pe) seen immediately after errors were analyzed. The results show that the amplitude of the Ne/ERN was reduced significantly following sleep deprivation. Reduction also occurred for error trials with subsequent correction, indicating that sleep deprivation influenced error correction ability. This study further demonstrated that the impairment in immediate error correction following sleep deprivation was confined to specific stimulus types, with both Ne/ERN and behavioral correction rates being reduced only for trials in which flanker stimuli were incongruent with the target stimulus, while the response to the target was compatible with that of the flanker stimuli following sleep deprivation. The results thus warrant future systematic investigation of the interaction between stimulus type and error correction following sleep deprivation. PMID:17542943

  3. Synergistic killing effect of chloroquine and androgen deprivation in LNCaP cells

    SciTech Connect

    Kaini, Ramesh R.; Hu, Chien-An A.

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Chloroquine synergistically killed LNCaP cells during androgen deprivation treatment. Black-Right-Pointing-Pointer Chloroquine inhibited the function of autolysosomes and decreases the cytosolic ATP. Black-Right-Pointing-Pointer Chloroquine induced nuclear and DNA fragmentation in androgen deprived LNCaP. Black-Right-Pointing-Pointer Chloroquine may be an useful adjuvant in hormone ablation therapy in PCa patients. -- Abstract: Modulation of autophagy is a new paradigm in cancer therapeutics. Recently a novel function of chloroquine (CLQ) in inhibiting degradation of autophagic vesicles has been revealed, which raises the question whether CLQ can be used as an adjuvant in targeting autophagic pro-survival mechanism in prostate cancer (PCa). We previously showed that autophagy played a protective role during hormone ablation therapy, in part, by consuming lipid droplets in PCa cells. In addition, blocking autophagy by genetic and pharmacological means in the presence of androgen deprivation caused cell death in PCa cells. To further investigate the importance of autophagy in PCa survival and dissect the role of CLQ in PCa death, we treated hormone responsive LNCaP cells with CLQ in combination with androgen deprivation. We observed that CLQ synergistically killed LNCaP cells during androgen deprivation in a dose- and time-dependent manner. We further confirmed that CLQ inhibited the maturation of autophagic vesicles and decreased the cytosolic ATP. Moreover, CLQ induced nuclear condensation and DNA fragmentation, a hallmark of apoptosis, in androgen deprived LNCaP cells. Taken together, our finding suggests that CLQ may be an useful adjuvant in hormone ablation therapy to improve the therapeutic efficacy.

  4. Reduced Cardiovascular Capacity and Resting Metabolic Rate in Men with Prostate Cancer Undergoing Androgen Deprivation: A Comprehensive Cross-Sectional Investigation

    PubMed Central

    Wall, Bradley A.; Galvão, Daniel A.; Fatehee, Naeem; Taaffe, Dennis R.; Spry, Nigel; Joseph, David; Newton, Robert U.

    2015-01-01

    Objectives. To investigate if androgen deprivation therapy exposure is associated with additional risk factors for cardiovascular disease and metabolic treatment-related toxicities. Methods. One hundred and seven men (42–89 years) with prostate cancer undergoing androgen deprivation therapy completed a maximal graded objective exercise test to determine maximal oxygen uptake, assessments for resting metabolic rate, body composition, blood pressure and arterial stiffness, and blood biomarker analysis. A cross-sectional analysis was undertaken to investigate the potential impact of therapy exposure with participants stratified into two groups according to duration of androgen deprivation therapy (<3 months and ≥3 months). Results. Maximal oxygen uptake (26.1 ± 6.0 mL/kg/min versus 23.2 ± 5.8 mL/kg/min, p = 0.020) and resting metabolic rate (1795 ± 256 kcal/d versus 1647 ± 236 kcal/d, p = 0.005) were significantly higher in those with shorter exposure to androgen deprivation. There were no differences between groups for peripheral and central blood pressure, arterial stiffness, or metabolic profile. Conclusion. Three months or longer exposure to androgen deprivation therapy was associated with reduced cardiorespiratory capacity and resting metabolic rate, but not in a range of blood biomarkers. These findings suggest that prolonged exposure to androgen deprivation therapy is associated with negative alterations in cardiovascular outcomes. Trial registry is: ACTRN12609000200280. PMID:26587019

  5. SOCIODEMOGRAPHIC DOMAINS OF DEPRIVATION AND PRETERM BIRTH

    EPA Science Inventory

    Area-level deprivation is consistently associated with poor health outcomes. Using US census data (2000) and principal components analysis, a priori defined socio-demographic indices of poverty, housing, residential stability, occupation, employment and education were created fo...

  6. Dream Deprivation and Facilitation with Hypnosis

    ERIC Educational Resources Information Center

    Albert, Ira B.; Boone, Donald

    1975-01-01

    The present study attempted to deprive human subjects of dreaming through the administration of a posthypnotic suggestion and to increase or facilitate dreaming through a second suggestion that was used with another group of subjects. (Author/RK)

  7. Relative deprivation and mortality in South Africa.

    PubMed

    Salti, Nisreen

    2010-03-01

    This paper tests the relative income hypothesis by considering the relationship between mortality, income and relative deprivation in South Africa using individual-level data on income and five measures of relative deprivation each with a different reference group. We find that income tends to be protective of, and relative deprivation detrimental to health, but the latter often gives a better account of mortality than does income alone. For some population groups the fit is improved in specifications which include both income and relative deprivation. Overall, there seems to be solid evidence in support of the relative income hypothesis, particularly for the more economically disadvantaged population groups. Relative deprivation is especially significant when age is the reference group, suggesting that the comparison of socio-economic standing that has an impact on health tends to happen within cohorts. The results are robust to splitting the sample into urban/rural subsamples and to looking at the incidence of illness as the health outcome rather than mortality. While little is known about the mechanisms underlying the effect of relative deprivation on health and mortality, the consistent evidence in favor of age as a reference group, particularly in a context like South Africa's suggests that intra-cohort comparisons should be an avenue for more in depth investigation. PMID:20045239

  8. Prostate Cancer Severity Associations with Neighborhood Deprivation

    PubMed Central

    Zeigler-Johnson, Charnita M.; Tierney, Ann; Rebbeck, Timothy R.; Rundle, Andrew

    2011-01-01

    Background. The goal of this paper was to examine neighborhood deprivation and prostate cancer severity. Methods. We studied African American and Caucasian prostate cancer cases from the Pennsylvania State Cancer Registry. Census tract-level variables and deprivation scores were examined in relation to diagnosis stage, grade, and tumor aggressiveness. Results. We observed associations of low SES with high Gleason score among African Americans residing in neighborhoods with low educational attainment (OR = 1.34, 95% CI = 1.13–1.60), high poverty (OR = 1.39, 95% CI = 1.15–1.67), low car ownership (OR = 1.46, 95% CI = 1.20–1.78), and higher percentage of residents on public assistance (OR = 1.32, 95% = 1.08–1.62). The highest quartile of neighborhood deprivation was also associated with high Gleason score. For both Caucasians and African Americans, the highest quartile of neighborhood deprivation was associated with high Gleason score at diagnosis (OR = 1.34, 95% CI = 1.19–1.52; OR = 1.71, 95% CI = 1.21–2.40, resp.). Conclusion. Using a neighborhood deprivation index, we observed associations between high-grade prostate cancer and neighborhood deprivation in Caucasians and African-Americans. PMID:22111000

  9. Neighbourhood Deprivation, School Disorder and Academic Achievement in Primary Schools in Deprived Communities in England

    ERIC Educational Resources Information Center

    Barnes, Jacqueline; Belsky, Jay; Broomfield, Kate A.; Melhuish, Edward

    2006-01-01

    There is growing concern about violent behaviour in schools, involving students, staff and/or parents. A survey of 1777 primary schools (for children aged 5 to 11) throughout England, most in areas of social and economic deprivation, found more disorder in neighbourhoods with greater deprivation. More disorder was also observed when there was more…

  10. Disentangling Area Effects: Evidence from Deprived and Non-Deprived Neighbourhoods.

    ERIC Educational Resources Information Center

    Atkinson, Rowland; Kintrea, Keith

    2001-01-01

    Investigated whether living in a deprived area compounded residents' disadvantaged status and whether area effects contributed to social exclusion. Data from surveys conducted in deprived and socially mixed neighborhoods indicated that both structure and agency were important in influencing neighborhood problems, though living in areas of…

  11. Deprivation and outcome of total knee replacement.

    PubMed

    Murray, James R D; Birdsall, Paul D; Sher, J Lester; Deehan, David J

    2006-03-01

    Deprivation correlates with poor health and psychosocial variables can affect the symptoms of knee arthritis. Our aim was to determine the effect of deprivation on the level of knee function and health-related quality of life at the time of arthroplasty and 12 months after total knee replacement. From our database of over 2500 knee replacements, we analysed both clinical and quality of life outcome measures. We analysed the relationship between deprivation (by Townsend score), knee function (Knee Society Score) and health-related quality of life (Nottingham Health Profile) before total knee replacement (TKR) and at 12 months post-operation. There was no significant correlation between Townsend score, Knee Society Score and Nottingham Health Profile preoperatively or at 12 months after knee replacement, thus showing that there was no association between deprivation and the severity of knee arthritis at the time of joint replacement nor was there a relationship between deprivation and the short-term outcome from total knee replacement. PMID:16469499

  12. Abscisic Acid in relation to mineral deprivation.

    PubMed

    Mizrahi, Y; Richmond, A E

    1972-12-01

    Tobacco (Nicotiana rustica) plants growing in half-strength Hoagland solution were deprived of nutrients by being transferred to distilled water. The abscisic acid content of leaves in the mineral-deprived plants rose continuously throughout the 7 days of the experimental period. However, although the content of ABA rose within 24 hours, a decline in growth and leaf-chlorophyll were discernible only after the 4th day of mineral deprivation. As anticipated, mineral-deprived (stressed) plants exhibit "resistance" to lack of aeration in the root medium, similar to that shown in salt-stressed plants or plants that were pretreated with absiscic acid. When the mineral-deprived plants were returned to half-strength Hoagland, the content of leaf abscisic acid declined to the prestressed level and the "resistance" to lack of root aeration disappeared.These results indicate that an increase in abscisic acid may be induced by conditions unfavorable to growth and not exclusively by conditions affecting the plant's water balance. In addition, the work also indicates that mineral deficiency is associated with significant modification in the hormonal balance of the plant. PMID:16658239

  13. Deprivation amblyopia and congenital hereditary cataract.

    PubMed

    Mansouri, Behzad; Stacy, Rebecca C; Kruger, Joshua; Cestari, Dean M

    2013-01-01

    Amblyopia is a neurodevelopmental disorder of vision associated with decreased visual acuity, poor or absent stereopsis, and suppression of information from one eye.(1,2) Amblyopia may be caused by strabismus (strabismic amblyopia), refractive error (anisometropic amblyopia), or deprivation from obstructed vision (deprivation amblyopia). 1 In the developed world, amblyopia is the most common cause of childhood visual impairment, 3 which reduces quality of life 4 and also almost doubles the lifetime risk of legal blindness.(5, 6) Successful treatment of amblyopia greatly depends on early detection and treatment of predisposing disorders such as congenital cataract, which is the most common cause of deprivational amblyopia. Understanding the genetic causes of congenital cataract leads to more effective screening tests, early detection and treatment of infants and children who are at high risk for hereditary congenital cataract. PMID:24138041

  14. Final Report of Multicenter Canadian Phase III Randomized Trial of 3 Versus 8 Months of Neoadjuvant Androgen Deprivation Therapy Before Conventional-Dose Radiotherapy for Clinically Localized Prostate Cancer

    SciTech Connect

    Crook, Juanita Ludgate, Charles; Malone, Shawn; Perry, Gad; Eapen, Libni; Bowen, Julie; Robertson, Susan; Lockwood, Gina M.Math.

    2009-02-01

    Purpose: To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy before conventional-dose radiotherapy (RT) on disease-free survival for localized prostate cancer. Methods and Materials: Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before 66 Gy RT at four participating centers. The median baseline prostate-specific antigen level was 9.7 ng/mL (range, 1.3-189). Of the 378 men, 26% had low-, 43% intermediate-, and 31% high-risk disease. The two arms were balanced in terms of age, Gleason score, clinical T category, risk group, and presenting prostate-specific antigen level. The median follow-up for living patients was 6.6 years (range, 1.6-10.1). Of the 378 patients, 361 were evaluable, and 290 were still living. Results: The 5-year actuarial freedom from failure rate for the 3- vs. 8-month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in the failure types between the two arms. The median prostate-specific antigen level at the last follow-up visit for patients without treatment failure was 0.6 ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free survival rate at 5 years was improved for the high-risk patients in the 8-month arm (71% vs. 42%, p = 0.01). Conclusion: A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.

  15. Play Deprivation: Is It Happening In Your School?

    ERIC Educational Resources Information Center

    Lauer, Lisa M.

    2011-01-01

    High-stakes testing combined with the notion that indoor and outdoor spontaneous play are a "waste of time" have contributed to the condition known as "play deprivation". This paper defines the term play deprivation and explores its negative effects on children and adults. Negative effects resulting from play deprivation include an increase in…

  16. Economic Deprivation and Early-Childhood Development.

    ERIC Educational Resources Information Center

    Duncan, Greg J.; And Others

    This study used longitudinal data from the Infant Health and Development Program (IHDP) to examine three issues regarding effects of economic deprivation on child development: (1) the effects on children's developmental outcomes of poverty and such poverty correlates as single parenthood, ethnicity, and maternal education; (2) the developmental…

  17. ART FOR THE ECONOMICALLY AND SOCIALLY DEPRIVED.

    ERIC Educational Resources Information Center

    MCFEE, JUNE K.

    THERE ARE CULTURAL DIFFERENCES IN THE CHILDREN OF THE ECONOMICALLY DEPRIVED IN THE UNITED STATES. ART EDUCATION CAN HELP THESE CHILDREN DEAL WITH THEIR ENVIRONMENT. EXAMPLES OF ETHNIC DIVERSITY ARE GIVEN IN REPORTS ON THE CHARACTERISTICS OF SPANISH SPEAKING PEOPLE (MEXICAN-AMERICANS, PUERTO RICANS, AND FILIPINOS), NEGROES, AND AMERICAN INDIANS.…

  18. Relative Deprivation and the Gender Wage Gap.

    ERIC Educational Resources Information Center

    Jackson, Linda A.

    1989-01-01

    Discusses how gender differences in the value of pay, based on relative deprivation theory, explain women's paradoxical contentment with lower wages. Presents a model of pay satisfaction to integrate value-based and comparative-referent explanations of the relationship between gender and pay satisfaction. Discusses economic approaches to the…

  19. Degradation of Binocular Coordination during Sleep Deprivation

    PubMed Central

    Tong, Jianliang; Maruta, Jun; Heaton, Kristin J.; Maule, Alexis L.; Rajashekar, Umesh; Spielman, Lisa A.; Ghajar, Jamshid

    2016-01-01

    To aid a clear and unified visual perception while tracking a moving target, both eyes must be coordinated, so the image of the target falls on approximately corresponding areas of the fovea of each eye. The movements of the two eyes are decoupled during sleep, suggesting a role of arousal in regulating binocular coordination. While the absence of visual input during sleep may also contribute to binocular decoupling, sleepiness is a state of reduced arousal that still allows for visual input, providing a context within which the role of arousal in binocular coordination can be studied. We examined the effects of sleep deprivation on binocular coordination using a test paradigm that we previously showed to be sensitive to sleep deprivation. We quantified binocular coordination with the SD of the distance between left and right gaze positions on the screen. We also quantified the stability of conjugate gaze on the target, i.e., gaze–target synchronization, with the SD of the distance between the binocular average gaze and the target. Sleep deprivation degraded the stability of both binocular coordination and gaze–target synchronization, but between these two forms of gaze control the horizontal and vertical components were affected differently, suggesting that disconjugate and conjugate eye movements are under different regulation of attentional arousal. The prominent association found between sleep deprivation and degradation of binocular coordination in the horizontal direction may be used for a fit-for-duty assessment. PMID:27379009

  20. Infant Face Preferences after Binocular Visual Deprivation

    ERIC Educational Resources Information Center

    Mondloch, Catherine J.; Lewis, Terri L.; Levin, Alex V.; Maurer, Daphne

    2013-01-01

    Early visual deprivation impairs some, but not all, aspects of face perception. We investigated the possible developmental roots of later abnormalities by using a face detection task to test infants treated for bilateral congenital cataract within 1 hour of their first focused visual input. The seven patients were between 5 and 12 weeks old…

  1. Parental Deprivation and the Development of Aggression.

    ERIC Educational Resources Information Center

    Mitchell, G.

    The research on parental deprivation done at the Wisconsin primate laboratories and related laboratories is summarized. Social isolation and certain other social conditions were observed in their effects on aggressive behavior. Isolate-reared rhesus monkeys show more abnormality in postures and movements than do socially reared monkeys from…

  2. Degradation of Binocular Coordination during Sleep Deprivation.

    PubMed

    Tong, Jianliang; Maruta, Jun; Heaton, Kristin J; Maule, Alexis L; Rajashekar, Umesh; Spielman, Lisa A; Ghajar, Jamshid

    2016-01-01

    To aid a clear and unified visual perception while tracking a moving target, both eyes must be coordinated, so the image of the target falls on approximately corresponding areas of the fovea of each eye. The movements of the two eyes are decoupled during sleep, suggesting a role of arousal in regulating binocular coordination. While the absence of visual input during sleep may also contribute to binocular decoupling, sleepiness is a state of reduced arousal that still allows for visual input, providing a context within which the role of arousal in binocular coordination can be studied. We examined the effects of sleep deprivation on binocular coordination using a test paradigm that we previously showed to be sensitive to sleep deprivation. We quantified binocular coordination with the SD of the distance between left and right gaze positions on the screen. We also quantified the stability of conjugate gaze on the target, i.e., gaze-target synchronization, with the SD of the distance between the binocular average gaze and the target. Sleep deprivation degraded the stability of both binocular coordination and gaze-target synchronization, but between these two forms of gaze control the horizontal and vertical components were affected differently, suggesting that disconjugate and conjugate eye movements are under different regulation of attentional arousal. The prominent association found between sleep deprivation and degradation of binocular coordination in the horizontal direction may be used for a fit-for-duty assessment. PMID:27379009

  3. Relative Deprivation, Rising Expectations, and Black Militancy

    ERIC Educational Resources Information Center

    Abeles, Ronald P.

    1976-01-01

    Investigates the role of relative deprivation (RD) and rising expectations (RE) as mediating variables between social structure and black militancy through secondary analyses of survey data of blacks living in Cleveland and Miami in the late 1960s. Alternative explanations and implications derived from the present data and the theories for the…

  4. The Cycle of Deprivation: Myths and Misconceptions

    ERIC Educational Resources Information Center

    Welshman, John

    2008-01-01

    The year 2006 marked the 30th anniversary of the publication of Michael Rutter and Nicola Madge's Cycles of Disadvantage (1976). As such, it provides an opportunity to take stock of debates over an alleged cycle of deprivation, both in the 1970s, and more recently. This article seeks to use historical methods in order to outline some areas in…

  5. Effects of sleep deprivation on cognition.

    PubMed

    Killgore, William D S

    2010-01-01

    Sleep deprivation is commonplace in modern society, but its far-reaching effects on cognitive performance are only beginning to be understood from a scientific perspective. While there is broad consensus that insufficient sleep leads to a general slowing of response speed and increased variability in performance, particularly for simple measures of alertness, attention and vigilance, there is much less agreement about the effects of sleep deprivation on many higher level cognitive capacities, including perception, memory and executive functions. Central to this debate has been the question of whether sleep deprivation affects nearly all cognitive capacities in a global manner through degraded alertness and attention, or whether sleep loss specifically impairs some aspects of cognition more than others. Neuroimaging evidence has implicated the prefrontal cortex as a brain region that may be particularly susceptible to the effects of sleep loss, but perplexingly, executive function tasks that putatively measure prefrontal functioning have yielded inconsistent findings within the context of sleep deprivation. Whereas many convergent and rule-based reasoning, decision making and planning tasks are relatively unaffected by sleep loss, more creative, divergent and innovative aspects of cognition do appear to be degraded by lack of sleep. Emerging evidence suggests that some aspects of higher level cognitive capacities remain degraded by sleep deprivation despite restoration of alertness and vigilance with stimulant countermeasures, suggesting that sleep loss may affect specific cognitive systems above and beyond the effects produced by global cognitive declines or impaired attentional processes. Finally, the role of emotion as a critical facet of cognition has received increasing attention in recent years and mounting evidence suggests that sleep deprivation may particularly affect cognitive systems that rely on emotional data. Thus, the extent to which sleep deprivation

  6. Sleep deprivation produces feelings of vicarious agency.

    PubMed

    Hon, Nicholas; Poh, Jia-Hou

    2016-02-01

    A variety of self-related psychological constructs are supported by the fundamental ability to accurately sense either self-agency or lack of agency in some action or outcome. Agency judgments are typically studied in individuals who are well-rested and mentally-fresh; however, in our increasingly fast-paced world, such judgments often need to be made while in less optimal states. Here, we studied the effect of being in one such non-optimal state - when sleep-deprived - on judgments of agency. We found that 24h of total sleep deprivation elevated agency ratings on trials designed to produce a strong sense of non-agency. These data provide the first evidence that physiological state variables can affect agency processing in the normal population. PMID:26773604

  7. Maximal aerobic exercise following prolonged sleep deprivation.

    PubMed

    Goodman, J; Radomski, M; Hart, L; Plyley, M; Shephard, R J

    1989-12-01

    The effect of 60 h without sleep upon maximal oxygen intake was examined in 12 young women, using a cycle ergometer protocol. The arousal of the subjects was maintained by requiring the performance of a sequence of cognitive tasks throughout the experimental period. Well-defined oxygen intake plateaus were obtained both before and after sleep deprivation, and no change of maximal oxygen intake was observed immediately following sleep deprivation. The endurance time for exhausting exercise also remained unchanged, as did such markers of aerobic performance as peak exercise ventilation, peak heart rate, peak respiratory gas exchange ratio, and peak blood lactate. However, as in an earlier study of sleep deprivation with male subjects (in which a decrease of treadmill maximal oxygen intake was observed), the formula of Dill and Costill (4) indicated the development of a substantial (11.6%) increase of estimated plasma volume percentage with corresponding decreases in hematocrit and red cell count. Possible factors sustaining maximal oxygen intake under the conditions of the present experiment include (1) maintained arousal of the subjects with no decrease in peak exercise ventilation or the related respiratory work and (2) use of a cycle ergometer rather than a treadmill test with possible concurrent differences in the impact of hematocrit levels and plasma volume expansion upon peak cardiac output and thus oxygen delivery to the working muscles. PMID:2628360

  8. Economic deprivation and early childhood development.

    PubMed

    Duncan, G J; Brooks-Gunn, J; Klebanov, P K

    1994-04-01

    We consider 3 questions regarding the effects of economic deprivation on child development. First, how are developmental outcomes in childhood affected by poverty and such poverty correlates as single parenthood, ethnicity, and maternal education? Second, what are the developmental consequences of the duration and timing of family economic deprivation? And, third, what is the comparative influence of economic deprivation at the family and neighborhood level? We investigate these issues with longitudinal data from the Infant Health and Development Program. We find that family income and poverty status are powerful correlates of the cognitive development and behavior of children, even after accounting for other differences--in particular family structure and maternal schooling--between low- and high-income families. While the duration of poverty matters, its timing in early childhood does not. Age-5 IQs are found to be higher in neighborhoods with greater concentrations of affluent neighbors, while the prevalence of low-income neighbors appears to increase the incidence of externalizing behavior problems. PMID:7516849

  9. Relative Deprivation and Sickness Absence in Sweden

    PubMed Central

    Helgertz, Jonas; Hess, Wolfgang; Scott, Kirk

    2013-01-01

    Background: A high prevalence of sickness absence in many countries, at a substantial societal cost, underlines the importance to understand its determining mechanisms. This study focuses on the link between relative deprivation and the probability of sickness absence. Methods: 184,000 men and women in Sweden were followed between 1982 and 2001. The sample consists of working individuals between the ages of 19 and 65. The outcome is defined as experiencing more than 14 days of sickness absence during a year. Based on the complete Swedish population, an individual’s degree of relative deprivation is measured through income compared to individuals of the same age, sex, educational level and type. In accounting for the possibility that sickness absence and socioeconomic status are determined by common factors, discrete-time duration models were estimated, accounting for unobserved heterogeneity through random effects. Results: The results confirm that the failure to account for the dynamics of the individual’s career biases the influence from socioeconomic characteristics. Results consistently suggest a major influence from relative deprivation, with a consistently lower risk of sickness absence among the highly educated. Conclusions: Altering individual’s health behavior through education appears more efficient in reducing the reliance on sickness absence, rather than redistributive policies. PMID:23996012

  10. A prospective study of septicaemia in colostrum-deprived foals.

    PubMed

    Robinson, J A; Allen, G K; Green, E M; Fales, W H; Loch, W E; Wilkerson, C G

    1993-05-01

    Fourteen mares and their foals were attended at parturition. After mare-foal bonding, 8 colostrum-deprived (CD) foals were removed from their dams, deprived of colostrum, and provided with an alternative milk source for the first 24 h of life. The mares were milked out every 2-4 h during this period to remove colostrum, after which the CD foals were returned to their mares and allowed to nurse. Six colostrum-fed (CF) foals were allowed to suck colostrum in the normal manner. Foal serum IgG concentration was determined by single radial immunodiffusion (means, CD = 0 mg/dl; CF = 1,508 mg/dl). Accepted methods were used to minimise infections in the neonatal foals. Of the 8 CD foals, 7 demonstrated clinical signs of sepsis. Septicaemia was confirmed in 5 of the 7 septicaemic CD foals by ante-mortem blood culture or by culture of tissue at necropsy. Organisms isolated included: Actinobacillus equuli, Escherichia coli, undifferentiated coliforms, Pseudomonas spp., and Actinomyces pyogenes. Clinically ill foals were treated with antimicrobial drugs, intravenous fluid therapy, flunixin meglumine, and anti-endotoxin hyperimmune serum. Three septicaemic CD foals survived. Four of 7 septicaemic CD foals died or were destroyed. Post-mortem lesions included bacterial embolic pneumonia, glomerulonephritis/nephritis, lymphoid depletion/atrophy, splenic and lymphoid necrosis, hepatitis, septic arthritis, and systemic bacterial embolism. None of the CF foals became septicaemic. One CF foal had foal heat diarrhoea and 1 CF foal had a serum IgG concentration of 160 mg/dl (i.e. failure of passive transfer), but both foals were otherwise normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8508750

  11. The growth of human HIV-1 infected U937 cells in immune-deprived mice.

    PubMed

    Chernukhin, I V; Chepurnov, A A; Gaidul, K V

    1995-01-01

    We report in vivo growth of human promonocytic cells infected with HIV-1 presented in new mouse model. Cloned U937 cells chronically infected with HIV-1 were grafted in (CBA*C57B1/6)F1 mice deprived of immunity by thymectomia and total body irradiation with subsequent marrow reconstitution. Nine weeks after cell inoculation, HIV-1-positive cells were found only in mice that received an additional single dose of cyclophosphamide (100 mg/kg bw) prior to transplantation, whereas, in mice without further immune deprivation, the complete elimination of cells bearing viral antigen occurred already on the seventh day after transplantation. The approach described may be suitable for in vivo development of antiviral drugs against latent infection in macrophage-like cells which represent a serious problem in therapy of AIDS in humans. PMID:8562863

  12. Augmented Reality as a Countermeasure for Sleep Deprivation.

    PubMed

    Baumeister, James; Dorrlan, Jillian; Banks, Siobhan; Chatburn, Alex; Smith, Ross T; Carskadon, Mary A; Lushington, Kurt; Thomas, Bruce H

    2016-04-01

    Sleep deprivation is known to have serious deleterious effects on executive functioning and job performance. Augmented reality has an ability to place pertinent information at the fore, guiding visual focus and reducing instructional complexity. This paper presents a study to explore how spatial augmented reality instructions impact procedural task performance on sleep deprived users. The user study was conducted to examine performance on a procedural task at six time points over the course of a night of total sleep deprivation. Tasks were provided either by spatial augmented reality-based projections or on an adjacent monitor. The results indicate that participant errors significantly increased with the monitor condition when sleep deprived. The augmented reality condition exhibited a positive influence with participant errors and completion time having no significant increase when sleep deprived. The results of our study show that spatial augmented reality is an effective sleep deprivation countermeasure under laboratory conditions. PMID:26780802

  13. A New Model to Study Sleep Deprivation-Induced Seizure

    PubMed Central

    Lucey, Brendan P.; Leahy, Averi; Rosas, Regine; Shaw, Paul J.

    2015-01-01

    Background and Study Objectives: A relationship between sleep and seizures is well-described in both humans and rodent animal models; however, the mechanism underlying this relationship is unknown. Using Drosophila melanogaster mutants with seizure phenotypes, we demonstrate that seizure activity can be modified by sleep deprivation. Design: Seizure activity was evaluated in an adult bang-sensitive seizure mutant, stress sensitive B (sesB9ed4), and in an adult temperature sensitive seizure mutant seizure (seits1) under baseline and following 12 h of sleep deprivation. The long-term effect of sleep deprivation on young, immature sesB9ed4 flies was also assessed. Setting: Laboratory. Participants: Drosophila melanogaster. Interventions: Sleep deprivation. Measurements and Results: Sleep deprivation increased seizure susceptibility in adult sesB9ed4/+ and seits1 mutant flies. Sleep deprivation also increased seizure susceptibility when sesB was disrupted using RNAi. The effect of sleep deprivation on seizure activity was reduced when sesB9ed4/+ flies were given the anti-seizure drug, valproic acid. In contrast to adult flies, sleep deprivation during early fly development resulted in chronic seizure susceptibility when sesB9ed4/+ became adults. Conclusions: These findings show that Drosophila is a model organism for investigating the relationship between sleep and seizure activity. Citation: Lucey BP, Leahy A, Rosas R, Shaw PJ. A new model to study sleep deprivation-induced seizure. SLEEP 2015;38(5):777–785. PMID:25515102

  14. The premack principle, response deprivation, and establishing operations

    PubMed Central

    Klatt, Kevin P.; Morris, Edward K.

    2001-01-01

    This paper describes response deprivation as an establishing operation. In this context, we review the concept of establishing operation, in particular, its reinforcer-establishing and evocative effects; we place response deprivation in the literature on the reinforcing effects of behavioral activity, wherein response deprivation subsumes the Premack principle; we describe the reinforcer-altering and evocative effects of response deprivation; and we address a methodological concern about the evocative effect. In closing, we discuss some conceptual and empirical implications of the foregoing analyses. PMID:22478362

  15. Crime: social disorganization and relative deprivation.

    PubMed

    Kawachi, I; Kennedy, B P; Wilkinson, R G

    1999-03-01

    Crime is seldom considered as an outcome in public health research. Yet major theoretical and empirical developments in the field of criminology during the past 50 years suggest that the same social environmental factors which predict geographic variation in crime rates may also be relevant for explaining community variations in health and wellbeing. Understanding the causes of variability in crime across countries and across regions within a country will help us to solve one of the enduring puzzles in public health, viz. why some communities are healthier than others. The purpose of this paper is to present a conceptual framework for investigating the influence of the social context on community health, using crime as the indicator of collective wellbeing. We argue that two sets of societal characteristics influence the level of crime: the degree of relative deprivation in society (for instance, measured by the extent of income inequality), and the degree of cohesiveness in social relations among citizens (measured, for instance, by indicators of 'social capital' and 'collective efficacy'). We provided a test of our conceptual framework using state-level ecologic data on violent crimes and property crimes within the USA. Violent crimes (homicide, assault, robbery) were consistently associated with relative deprivation (income inequality) and indicators of low social capital. Among property crimes, burglary was also associated with deprivation and low social capital. Areas with high crime rates tend also to exhibit higher mortality rates from all causes, suggesting that crime and population health share the same social origins. Crime is thus a mirror of the quality of the social environment. PMID:10190635

  16. The politics of relative deprivation: A transdisciplinary social justice perspective.

    PubMed

    Fu, Mengzhu; Exeter, Daniel J; Anderson, Anneka

    2015-05-01

    Relative deprivation was defined by Townsend (1987, p. 125) as "a state of observable and demonstrable disadvantage, relative to the local community or the wider society or nation to which an individual, family or group belongs". This definition is widely used within social and health sciences to identify, measure, and explain forms of inequality in human societies based on material and social conditions. From a multi-disciplinary social science perspective, we conducted a systematic literature review of published material in English through online database searches and books since 1966. We review the concept and measurement of relative 'deprivation' focussing on area-based deprivation in relation to inequities in health and social outcomes. This paper presents a perspective based in Aotearoa/New Zealand where colonisation has shaped the contours of racialised health inequities and current applications and understandings of 'deprivation'. We provide a critique of Townsend's concept of deprivation and area-based deprivation through a critical, structural analysis and suggest alternatives to give social justice a better chance. Deprivation measures used without critical reflection can lead to deficit framing of populations and maintain current inequities in health and social outcomes. We contend therefore that the lack of consideration of (bio)power, privilege, epistemology and (bio)politics is a central concern in studies of deprivation. Our review highlights the need for the academy to balance the asymmetry between qualitative and quantitative studies of deprivation through trans-disciplinary approaches to understanding deprivation, and subsequently, social and health inequities. We recommend that deprivation research needs be critically applied through a decolonising lens to avoid deficit framing and suggest that there is space for a tool that focuses on measuring the unequal distribution of power and privilege in populations. PMID:25547207

  17. BDNF in sleep, insomnia, and sleep deprivation.

    PubMed

    Schmitt, Karen; Holsboer-Trachsler, Edith; Eckert, Anne

    2016-01-01

    The protein brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors involved in plasticity of neurons in several brain regions. There are numerous evidence that BDNF expression is decreased by experiencing psychological stress and that, accordingly, a lack of neurotrophic support causes major depression. Furthermore, disruption in sleep homeostatic processes results in higher stress vulnerability and is often associated with stress-related mental disorders. Recently, we reported, for the first time, a relationship between BDNF and insomnia and sleep deprivation (SD). Using a biphasic stress model as explanation approach, we discuss here the hypothesis that chronic stress might induce a deregulation of the hypothalamic-pituitary-adrenal system. In the long-term it leads to sleep disturbance and depression as well as decreased BDNF levels, whereas acute stress like SD can be used as therapeutic intervention in some insomniac or depressed patients as compensatory process to normalize BDNF levels. Indeed, partial SD (PSD) induced a fast increase in BDNF serum levels within hours after PSD which is similar to effects seen after ketamine infusion, another fast-acting antidepressant intervention, while traditional antidepressants are characterized by a major delay until treatment response as well as delayed BDNF level increase. Key messages Brain-derived neurotrophic factor (BDNF) plays a key role in the pathophysiology of stress-related mood disorders. The interplay of stress and sleep impacts on BDNF level. Partial sleep deprivation (PSD) shows a fast action on BDNF level increase. PMID:26758201

  18. Relative Deprivation and Adolescent Outcomes in Iceland: A Multilevel Test

    ERIC Educational Resources Information Center

    Bernburg, Jon Gunnar; Thorlindsson, Thorolfur; Sigfusdottir, Inga Dora

    2009-01-01

    The theory of relative deprivation emphasizes that social comparisons contextualize how people experience impoverishment. An important application of this theory argues that relative deprivation that stems from unfavorable social comparisons can result in anger, normlessness and an increased likelihood of deviant behavior. We test this theory in a…

  19. Acute phase proteins response to feed deprivation in broiler chickens.

    PubMed

    Najafi, P; Zulkifli, I; Soleimani, A F; Goh, Y M

    2016-04-01

    Feed deprivation in poultry farming imposes some degree of stress to the birds, and adversely affects their well -being. Serum levels of acute phase proteins (APP) are potential physiological indicators of stress attributed to feed deprivation. However, it has not been determined how long it takes for a measurable APP response to stressors to occur in avian species. An experiment was designed to delineate the APP and circulating levels of corticosterone responses in commercial broiler chickens to feed deprivation for 30 h. It was hypothesized that feed deprivation would elicit both APP and corticosterone (CORT) reactions within 30 h that is probably associated with stress of hunger. Twenty-one day old birds were subjected to one of 5 feed deprivation periods: 0 (ad libitum, AL), 6, 12, 18, 24, and 30 h. Upon completion of the deprivation period, blood samples were collected to determine serum CORT, ovotransferrin (OVT), α1-acid glycoprotein (AGP), and ceruloplasmin (CP) concentrations. Results showed that feed deprivation for 24 h or more caused a marked elevation in CORT (P=0.002 and P<0.0001, respectively) when compared to AL. However, increases in AGP (P=0.0005), CP (P=0.0002), and OVT (P=0.0003) were only noted following 30 h of feed deprivation. It is concluded that elicitation of AGP, CP, and OVT response may represent a more chronic stressful condition than CORT response in assessing the well-being of broiler chickens. PMID:26908886

  20. 42 CFR 35.3 - Noncompliance; deprivation of privileges.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Noncompliance; deprivation of privileges. 35.3 Section 35.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.3 Noncompliance; deprivation of privileges....

  1. 42 CFR 35.3 - Noncompliance; deprivation of privileges.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Noncompliance; deprivation of privileges. 35.3 Section 35.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.3 Noncompliance; deprivation of privileges....

  2. 42 CFR 35.3 - Noncompliance; deprivation of privileges.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Noncompliance; deprivation of privileges. 35.3 Section 35.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.3 Noncompliance; deprivation of privileges....

  3. 42 CFR 35.3 - Noncompliance; deprivation of privileges.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Noncompliance; deprivation of privileges. 35.3 Section 35.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.3 Noncompliance; deprivation of privileges....

  4. 42 CFR 35.3 - Noncompliance; deprivation of privileges.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Noncompliance; deprivation of privileges. 35.3 Section 35.3 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICAL CARE AND EXAMINATIONS HOSPITAL AND STATION MANAGEMENT General § 35.3 Noncompliance; deprivation of privileges....

  5. Tempol prevents chronic sleep-deprivation induced memory impairment.

    PubMed

    Alzoubi, Karem H; Khabour, Omar F; Albawaana, Amal S; Alhashimi, Farah H; Athamneh, Rabaa Y

    2016-01-01

    Sleep deprivation is associated with oxidative stress that causes learning and memory impairment. Tempol is a nitroxide compound that promotes the metabolism of many reactive oxygen species (ROS) and has antioxidant and neuroprotective effect. The current study investigated whether chronic administration of tempol can overcome oxidative stress and prevent learning and memory impairment induced by sleep deprivation. Sleep deprivation was induced in rats using multiple platform model. Tempol was administered to rats via oral gavages. Behavioral studies were conducted to test the spatial learning and memory using radial arm water maze. The hippocampus was dissected; antioxidant biomarkers (GSH, GSSG, GSH/GSSG ratio, GPx, SOD, and catalase) were assessed. The result of this project revealed that chronic sleep deprivation impaired both short and long term memory (P<0.05), while tempol treatment prevented such effect. Furthermore, tempol normalized chronic sleep deprivation induced reduction in the hippocampus activity of catalase, GPx, and SOD (P<0.05). Tempol also enhanced the ratio of GSH/GSSG in chronically sleep deprived rats treated with tempol as compared with only sleep deprived rats (P<0.05). In conclusion chronic sleep deprivation induced memory impairment, and treatment with tempol prevented this impairment probably through normalizing antioxidant mechanisms in the hippocampus. PMID:26616531

  6. Small Area Indices of Multiple Deprivation in South Africa

    ERIC Educational Resources Information Center

    Noble, Michael; Barnes, Helen; Wright, Gemma; Roberts, Benjamin

    2010-01-01

    This paper presents the Provincial Indices of Multiple Deprivation that were constructed by the authors at ward level using 2001 Census data for each of South Africa's nine provinces. The principles adopted in conceptualising the indices are described and multiple deprivation is defined as a weighted combination of discrete dimensions of…

  7. Sleep Deprivation, Allergy Symptoms, and Negatively Reinforced Problem Behavior.

    ERIC Educational Resources Information Center

    Kennedy, Craig H.; Meyer, Kim A.

    1996-01-01

    A study of the relationship between presence or absence of sleep deprivation, allergy symptoms, and the rate and function of problem behavior in three adolescents with moderate to profound mental retardation found that problem behavior was negatively reinforced by escape from instruction, and both allergy symptoms and sleep deprivation influenced…

  8. Arginine deprivation using pegylated arginine deiminase has activity against primary acute myeloid leukemia cells in vivo.

    PubMed

    Miraki-Moud, Farideh; Ghazaly, Essam; Ariza-McNaughton, Linda; Hodby, Katharine A; Clear, Andrew; Anjos-Afonso, Fernando; Liapis, Konstantinos; Grantham, Marianne; Sohrabi, Fareeda; Cavenagh, Jamie; Bomalaski, John S; Gribben, John G; Szlosarek, Peter W; Bonnet, Dominique; Taussig, David C

    2015-06-25

    The strategy of enzymatic degradation of amino acids to deprive malignant cells of important nutrients is an established component of induction therapy of acute lymphoblastic leukemia. Here we show that acute myeloid leukemia (AML) cells from most patients with AML are deficient in a critical enzyme required for arginine synthesis, argininosuccinate synthetase-1 (ASS1). Thus, these ASS1-deficient AML cells are dependent on importing extracellular arginine. We therefore investigated the effect of plasma arginine deprivation using pegylated arginine deiminase (ADI-PEG 20) against primary AMLs in a xenograft model and in vitro. ADI-PEG 20 alone induced responses in 19 of 38 AMLs in vitro and 3 of 6 AMLs in vivo, leading to caspase activation in sensitive AMLs. ADI-PEG 20-resistant AMLs showed higher relative expression of ASS1 than sensitive AMLs. This suggests that the resistant AMLs survive by producing arginine through this metabolic pathway and ASS1 expression could be used as a biomarker for response. Sensitive AMLs showed more avid uptake of arginine from the extracellular environment consistent with their auxotrophy for arginine. The combination of ADI-PEG 20 and cytarabine chemotherapy was more effective than either treatment alone resulting in responses in 6 of 6 AMLs tested in vivo. Our data show that arginine deprivation is a reasonable strategy in AML that paves the way for clinical trials. PMID:25896651

  9. Effects of Sleep Deprivation on Dissociated Components of Executive Functioning

    PubMed Central

    Tucker, Adrienne M.; Whitney, Paul; Belenky, Gregory; Hinson, John M.; Van Dongen, Hans P.A.

    2010-01-01

    Study Objectives: We studied the effects of sleep deprivation on executive functions using a task battery which included a modified Sternberg task, a probed recall task, and a phonemic verbal fluency task. These tasks were selected because they allow dissociation of some important executive processes from non-executive components of cognition. Design: Subjects were randomized to a total sleep deprivation condition or a control condition. Performance on the executive functions task battery was assessed at baseline, after 51 h of total sleep deprivation (or no sleep deprivation in the control group), and following 2 nights of recovery sleep, at fixed time of day (11:00). Performance was also measured repeatedly throughout the experiment on a control task battery, for which the effects of total sleep deprivation had been documented in previously published studies. Setting: Six consecutive days and nights in a controlled laboratory environment with continuous behavioral monitoring. Participants: Twenty-three healthy adults (age range 22–38 y; 11 women). Twelve subjects were randomized to the sleep deprivation condition; the others were controls. Results: Performance on the control task battery was considerably degraded during sleep deprivation. Overall performance on the modified Sternberg task also showed impairment during sleep deprivation, as compared to baseline and recovery and compared to controls. However, two dissociated components of executive functioning on this task—working memory scanning efficiency and resistance to proactive interference—were maintained at levels equivalent to baseline. On the probed recall task, resistance to proactive interference was also preserved. Executive aspects of performance on the phonemic verbal fluency task showed improvement during sleep deprivation, as did overall performance on this task. Conclusion: Sleep deprivation affected distinct components of cognitive processing differentially. Dissociated non

  10. Total sleep deprivation decreases flow experience and mood status

    PubMed Central

    Kaida, Kosuke; Niki, Kazuhisa

    2014-01-01

    Background The purpose of this study was to examine the effect of sleep deprivation on flow experience. Methods Sixteen healthy male volunteers of mean age 21.4±1.59 (21–24) years participated in two experimental conditions, ie, sleep-deprivation and normal sleep. In the sleep-deprived condition, participants stayed awake at home for 36 hours (from 8 am until 10 pm the next day) beginning on the day prior to an experimental day. In both conditions, participants carried out a simple reaction time (psychomotor vigilance) task and responded to a questionnaire measuring flow experience and mood status. Results Flow experience was reduced after one night of total sleep deprivation. Sleep loss also decreased positive mood, increased negative mood, and decreased psychomotor performance. Conclusion Sleep deprivation has a strong impact on mental and behavioral states associated with the maintenance of flow, namely subjective well-being. PMID:24376356

  11. Comparisons and perceived deprivation in ethnic minority settings.

    PubMed

    Zagefka, Hanna; Brown, Rupert

    2005-04-01

    Two studies investigated comparison choices among ethnic minorities and majorities. The perceived status of the self vis-á-vis different comparison targets also was assessed. Antecedents and consequences of comparisons and relative deprivation were examined. Predictions were derived from social comparison, stigma, social identity, and relative deprivation research. Two surveys were conducted, one in London with mainly Asian participants (N = 235) and one in Germany with Turkish and Aussiedler participants (N = 166) and German majority members (N = 351). Participants preferred intragroup and temporal comparisons (with other ingroup members and with the self in the past) to various types of cross-group comparisons (with outgroup members). Perceived similarity and contact with a target positively predicted interest in comparing with this target, and perceived higher status of the target was a negative predictor. Some evidence was found that feelings of deprivation depend on comparison choices. Deprivation negatively predicted self-esteem and life satisfaction. Deprivation and group identification were negatively correlated. PMID:15743982

  12. DIFFERENCES IN THE TRANSCRIPTIONAL RESPONSE TO FULVESTRANT AND OESTROGEN DEPRIVATION IN ER-POSITIVE BREAST CANCER

    PubMed Central

    Patani, Neill; Dunbier, Anita; Anderson, Helen; Ghazoui, Zara; Ribas, Ricardo; Anderson, Elizabeth; Gao, Qiong; A’hern, Roger; Mackay, Alan; Lindemann, Justin; Wellings, Robert; Walker, Jill; Kuter, Irene; Martin, Lesley-Ann; Dowsett, Mitch

    2014-01-01

    Purpose Endocrine therapies include aromatase inhibitors and the selective oestrogen receptor (ER) down-regulator fulvestrant. This study aimed to determine if the reported efficacy of fulvestrant over anastrozole, and high- over low-dose fulvestrant, reflect distinct transcriptional responses. Experimental design Global gene expression profiles from ERα-positive breast carcinomas before and during pre-surgical treatment with fulvestrant (n=22) or anastrozole (n=81), and corresponding in vitro models, were compared. Transcripts responding differently to fulvestrant and oestrogen (E) deprivation were identified and integrated using gene ontology (GO), pathway and network analyses to evaluate their potential significance. Results The overall transcriptional response to fulvestrant and E-deprivation was correlated (r=0.61 in pre-surgical studies, r=0.87 in vitro), involving down-regulation of E-regulated and proliferation-associated genes. The transcriptional response to fulvestrant was of greater magnitude than E-deprivation (slope=0.62 in pre-surgical studies, slope=0.63 in vitro). Comparative analyses identified 28 genes and 40 GO categories affected specifically by fulvestrant. Seventeen fulvestrant-specific genes, including CAV1/2, SNAI2 and NRP1, associated with ERα, androgen receptor (AR) and TP53, in a network regulating cell cycle, death, survival, and tumour morphology. Eighteen genes responding differently to fulvestrant specifically predicted anti-proliferative response to fulvestrant, but not anastrozole. Transcriptional effects of low-dose fulvestrant correlated with high-dose treatment, but were of lower magnitude (ratio=0.29). Conclusions The transcriptional response to fulvestrant has much in common with E-deprivation, but is stronger with distinctions potentially attributable to arrest of E-independent ERα activity and involvement of AR signalling. Genes responding differently to fulvestrant may have predictive utility. These data are consistent

  13. Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase

    PubMed Central

    Bowles, Tawnya L.; Kim, Randie; Galante, Joseph; Parsons, Colin M.; Virudachalam, Subbulakshmi; Kung, Hsing-Jien; Bold, Richard J.

    2009-01-01

    Eukaryotic cells can synthesize the non-essential amino acid arginine from aspartate and citrulline using the enzyme argininosuccinate synthetase (ASS). It has been observed that ASS is under-expressed in various types of cancers ASS, for which arginine become auxotrophic. Arginine deiminase (ADI) is a prokaryotic enzyme that metabolizes arginine to citrulline and has been found to inhibit melanoma and hepatoma cancer cells deficient of ASS. We tested the hypothesis that pancreatic cancers have low ASS expression and therefore arginine deprivation by ADI will inhibit cell growth. ASS expression was examined in 47 malignant and 20 non-neoplastic pancreatic tissues as well as a panel of human pancreatic cancer cell lines. Arginine deprivation was achieved by treatment with a recombinant form of ADI formulated with polyethylene glycol (PEG-ADI). Effects on caspase activation, cell growth and cell death were examined. Furthermore, the effect of PEG-ADI on the in vivo growth of pancreatic xenografts was examined. Eighty-seven percent of the tumors lacked ASS expression; 5 of 7 cell lines similarly lacked ASS expression. PEG-ADI specifically inhibited growth of those cell lines lacking ASS. PEG-ADI treatment induced caspase activation and induction of apoptosis. PEG-ADI was well tolerated in mice despite complete elimination of plasma arginine; tumor growth was inhibited by ∼50%. Reduced expression of ASS occurs in pancreatic cancer and predicts sensitivity to arginine deprivation achieved by PEG-ADI treatment. Therefore, these findings suggest that arginine deprivation by ADI could provide a beneficial strategy for the treatment of pancreatic cancer, a malignancy in which new therapy is desperately needed. PMID:18661517

  14. Symptomatic zinc deficiency in experimental zinc deprivation.

    PubMed Central

    Taylor, C M; Goode, H F; Aggett, P J; Bremner, I; Walker, B E; Kelleher, J

    1992-01-01

    An evaluation of indices of poor zinc status was undertaken in five male subjects in whom dietary zinc intake was reduced from 85 mumol d-1 in an initial phase of the study to 14 mumol d-1. One of the subjects developed features consistent with zinc deficiency after receiving the low zinc diet for 12 days. These features included retroauricular acneform macullo-papular lesions on the face, neck, and shoulders and reductions in plasma zinc, red blood cell zinc, neutrophil zinc and plasma alkaline phosphatase activity. Alcohol induced hepatitis, which was suspected in this subject, may have caused a predisposition to altered zinc metabolism and possible zinc deficiency which was exacerbated by subsequent zinc deprivation. The report supports the value of neutrophil zinc concentration as an indicator of poor zinc status. PMID:1740525

  15. Sleep deprivation: Impact on cognitive performance

    PubMed Central

    Alhola, Paula; Polo-Kantola, Päivi

    2007-01-01

    Today, prolonged wakefulness is a widespread phenomenon. Nevertheless, in the field of sleep and wakefulness, several unanswered questions remain. Prolonged wakefulness can be due to acute total sleep deprivation (SD) or to chronic partial sleep restriction. Although the latter is more common in everyday life, the effects of total SD have been examined more thoroughly. Both total and partial SD induce adverse changes in cognitive performance. First and foremost, total SD impairs attention and working memory, but it also affects other functions, such as long-term memory and decision-making. Partial SD is found to influence attention, especially vigilance. Studies on its effects on more demanding cognitive functions are lacking. Coping with SD depends on several factors, especially aging and gender. Also interindividual differences in responses are substantial. In addition to coping with SD, recovering from it also deserves attention. Cognitive recovery processes, although insufficiently studied, seem to be more demanding in partial sleep restriction than in total SD. PMID:19300585

  16. Sleep deprivation attenuates inflammatory responses and ischemic cell death.

    PubMed

    Weil, Zachary M; Norman, Greg J; Karelina, Kate; Morris, John S; Barker, Jacqueline M; Su, Alan J; Walton, James C; Bohinc, Steven; Nelson, Randy J; DeVries, A Courtney

    2009-07-01

    Although the biological function of sleep remains uncertain, the consequences of sleep deprivation are well-described and are reported to be detrimental to cognitive function and affective well-being. Sleep deprivation also is strongly associated with elevated risk factors for cardiovascular disease. We used a mouse model of cardiac arrest/cardiopulmonary resuscitation to test the hypothesis that acute sleep deprivation would exacerbate neuroinflammation and neurodegeneration after global ischemia. The resulting data led to a rejection of our hypothesis that sleep deprivation is necessarily detrimental. Indeed, acute sleep deprivation (ASD) was associated with a reduction in ischemia-induced interleukin 1beta (IL-1beta) gene expression and attenuation of neuronal damage in the hippocampus. Further, sleep deprivation increased gene expression of two anti-inflammatory cytokines, IL-6 and IL-10 that are associated with improved ischemic outcome. To determine whether the anti-inflammatory properties of ASD were specific to ischemia, mice were treated systemically with lipopolysaccharide (LPS), a potent inflammogen. Acute sleep deprivation attenuated the central and peripheral increase in tumor necrosis factor-alpha (TNFalpha) and increased IL-10 expression. Together, the ischemia and LPS data suggest that, ASD produces an anti-inflammatory bias that could be exploited to improve medical procedures that are compromised by inflammation. PMID:19409382

  17. Spatial reversal learning is robust to total sleep deprivation.

    PubMed

    Leenaars, Cathalijn H C; Joosten, Ruud N J M A; Kramer, Michiel; Post, Ger; Eggels, Leslie; Wuite, Mark; Dematteis, Maurice; Feenstra, Matthijs G P; Van Someren, Eus J W

    2012-04-21

    Sleep deprivation affects cognitive functions that depend on the prefrontal cortex (PFC) such as cognitive flexibility, and the consolidation of newly learned information. The identification of cognitive processes that are either robustly sensitive or robustly insensitive to the same experimental sleep deprivation procedure, will allow us to better focus on the specific effects of sleep on cognition, and increase understanding of the mechanisms involved. In the present study we investigate whether sleep deprivation differentially affects the two separate cognitive processes of acquisition and consolidation of a spatial reversal task. After training on a spatial discrimination between two levers in a Skinner box, male Wistar rats were exposed to a reversal of the previously learned stimulus-response contingency. We first evaluated the effect of sleep deprivation on the acquisition of reversal learning. Performance on reversal learning after 12h of sleep deprivation (n=12) was compared to performance after control conditions (n=12). The second experiment evaluated the effect of sleep deprivation on the consolidation of reversal learning; the first session of reversal learning was followed by 3h of nap prevention (n=8) or undisturbed control conditions (n=8). The experiments had sufficient statistical power (0.90 and 0.81, respectively) to detect differences with medium effect sizes. Neither the acquisition, nor the consolidation, of reversal learning was affected by acute sleep deprivation. Together with previous findings, these results help to further delineate the role of sleep in cognitive processing. PMID:22321457

  18. Stress-free automatic sleep deprivation using air puffs

    PubMed Central

    Gross, Brooks A.; Vanderheyden, William M.; Urpa, Lea M.; Davis, Devon E.; Fitzpatrick, Christopher J.; Prabhu, Kaustubh; Poe, Gina R.

    2015-01-01

    Background Sleep deprivation via gentle handling is time-consuming and personnel-intensive. New Method We present here an automated sleep deprivation system via air puffs. Implanted EMG and EEG electrodes were used to assess sleep/waking states in six male Sprague-Dawley rats. Blood samples were collected from an implanted intravenous catheter every 4 hours during the 12-hour light cycle on baseline, 8 hours of sleep deprivation via air puffs, and 8 hours of sleep deprivation by gentle handling days. Results The automated system was capable of scoring sleep and waking states as accurately as our offline version (~90% for sleep) and with sufficient speed to trigger a feedback response within an acceptable amount of time (1.76 s). Manual state scoring confirmed normal sleep on the baseline day and sleep deprivation on the two manipulation days (68% decrease in non-REM, 63% decrease in REM, and 74% increase in waking). No significant differences in levels of ACTH and corticosterone (stress hormones indicative of HPA axis activity) were found at any time point between baseline sleep and sleep deprivation via air puffs. Comparison with Existing Method There were no significant differences in ACTH or corticosterone concentrations between sleep deprivation by air puffs and gentle handling over the 8-hour period. Conclusions Our system accurately detects sleep and delivers air puffs to acutely deprive rats of sleep with sufficient temporal resolution during the critical 4-5 h post learning sleep-dependent memory consolidation period. The system is stress-free and a viable alternative to existing sleep deprivation techniques. PMID:26014662

  19. Deprivation-induced cortical reorganization in children with cochlear implants.

    PubMed

    Sharma, Anu; Gilley, Phillip M; Dorman, Michael F; Baldwin, Robert

    2007-09-01

    A basic finding in developmental neurophysiology is that some areas of the cortex cortical areas will reorganize following a period of stimulus deprivation. In this review, we discuss mainly electroencephalography (EEG) studies of normal and deprivation-induced abnormal development of the central auditory pathways in children and in animal models. We describe age cut-off for sensitive periods for central auditory development in congenitally deaf children who are fitted with a cochlear implant. We speculate on mechanisms of decoupling and reorganization which may underlie the end of the sensitive period. Finally, we describe new magentoencephalography (MEG) evidence of somatosensory cross-modal plasticity following long-term auditory deprivation. PMID:17828665

  20. Teachers' perceptions of students' feelings of clothing deprivation.

    PubMed

    Francis, S K; Demissee, D W

    1993-06-01

    The purpose of this study was to compare teachers' perceptions of the feelings of perceived clothing deprivation among their students with the students' actual feelings. The samples consisted of 336 home economics students in Grades 9 through 12 from 6 high schools and 140 teachers employed by the same 6 schools. Results indicated that there was no difference between teachers and students on two measures of clothing deprivation, Inability to Buy and Clothing Deprivation Relative to Peers. In addition, a number of programs for meeting students' clothing needs were identified by the teachers. PMID:8337068

  1. Sleep Deprived and Sweating It Out: The Effects of Total Sleep Deprivation on Skin Conductance Reactivity to Psychosocial Stress

    PubMed Central

    Liu, Jean C.J.; Verhulst, Silvan; Massar, Stijn A.A.; Chee, Michael W.L.

    2015-01-01

    Study Objectives: We examined how sleep deprivation alters physiological responses to psychosocial stress by evaluating changes in skin conductance. Design: Between-subjects design with one group allocated to 24 h of total sleep deprivation and the other to rested wakefulness. Setting: The study took place in a research laboratory. Participants: Participants were 40 healthy young adults recruited from a university. Interventions: Sleep deprivation and feedback. Measurements and Results: Electrodermal activity was monitored while participants completed a difficult perceptual task with false feedback. All participants showed increased skin conductance levels following stress. However, compared to well-rested participants, sleep deprived participants showed higher skin conductance reactivity with increasing stress levels. Conclusions: Our results suggest that sleep deprivation augments allostatic responses to increasing psychosocial stress. Consequentially, we propose sleep loss as a risk factor that can influence the pathogenic effects of stress. Citation: Liu JC, Verhulst S, Massar SA, Chee MW. Sleep deprived and sweating it out: the effects of total sleep deprivation on skin conductance reactivity to psychosocial stress. SLEEP 2015;38(1):155–159. PMID:25325448

  2. Adverse Events Associated with Hormonal Therapy for Prostate Cancer

    PubMed Central

    Kumar, Ravi J; Barqawi, Al; Crawford, E. David

    2005-01-01

    With expanding indications for androgen deprivation therapy for the treatment of prostate cancer, it is imperative that health care providers be cognizant of the possible adverse effects of therapy, as well as their prevention and treatment. Neurologic and psychiatric effects include depression and declines in cognitive function. Musculoskeletal effects of hormonal therapy include osteoporosis, decrease in muscle mass, and fatigue. Gynecomastia, weight gain, and erectile dysfunction are also seen, as are hematologic effects. Further research is needed to evaluate alternative forms of therapy, such as intermittent hormonal deprivation and antiandrogen monotherapy. PMID:16985883

  3. A combined approach against tumorigenesis using glucose deprivation and mitochondrial complex 1 inhibition by rotenone.

    PubMed

    Agarwal, Nupur Rani; Maurya, Nancy; Pawar, Jogendra Singh; Ghosh, Ilora

    2016-07-01

    Cancer cells exhibit various degrees of mitochondrial metabolic alterations. Owing to their multiple roles, mitochondria are attractive target for cancer therapy. Cancerous cells have high glucose (HG) requirements for their growth. Depriving them of glucose has been an approach used in many studies to restrict their perpetuation. However, such deprivation can negatively affect the surrounding normal cells in vivo. Keeping this in view, we treated HeLa cells with only physiological glucose (PG, 5.5 mM) and a combination of physiological glucose with a very low dose (1 nM) of rotenone (PGT), taking high glucose (HG, 25 mM)-treated HeLa cells as normal. We demonstrated that HeLa cells under PG condition mainly exhibited growth arrest. The PGT combination induced apoptosis in HeLa cells by generation of ROS, decrease in ATP production even with around 1.89-fold increase in glucose consumption, cell cycle arrest at S-phase and substantial increase in sub-diploid (Sub-D) population. The oxidative stress generated in both PG and PGT conditions stabilised p53 by localising it in the nuclei of HeLa cells, which would have otherwise undergone HPV-mediated inactivation. Pre-mature senescence induced due to limited glucose availability was found to be regulated by nuclear translocated p53 which, in turn, induced p21, pAkt and pERK. The cyto-toxic effect of rotenone on glucose deprived HeLa cells, synergistically activated NFκB, caspase-3 and Bax along with reduced expression of hyaluronan, a ROS scavenging molecule on their cell surface. Thus, our finding might be a valuable approach to specifically target cancerous cells in a more physiologically feasible condition and can serve as a relevant biochemical basis to gain new insights into cancer therapy. PMID:27109893

  4. CCAAT/Enhancer binding protein β controls androgen-deprivation-induced senescence in prostate cancer cells.

    PubMed

    Barakat, D J; Zhang, J; Barberi, T; Denmeade, S R; Friedman, A D; Paz-Priel, I

    2015-11-26

    The processes associated with transition to castration-resistant prostate cancer (PC) growth are not well understood. Cellular senescence is a stable cell cycle arrest that occurs in response to sublethal stress. It is often overcome in malignant transformation to confer a survival advantage. CCAAT/Enhancer Binding Protein (C/EBP) β function is frequently deregulated in human malignancies and interestingly, androgen-sensitive PC cells express primarily the liver-enriched inhibitory protein isoform. We found that C/EBPβ expression is negatively regulated by androgen receptor (AR) activity and that treatment of androgen-sensitive cell lines with anti-androgens increases C/EBPβ mRNA and protein levels. Accordingly, we also find that C/EBPβ levels are significantly elevated in primary PC samples from castration-resistant compared with therapy-naive patients. Chromatin immunoprecipitation demonstrated enhanced binding of the AR to the proximal promoter of the CEBPB gene in the presence of dihydroxytestosterone. Upon androgen deprivation, induction of C/EBPβ is facilitated by active transcription as evident by increased histone 3 acetylation at the C/EBPβ promoter. Also, the androgen agonist R1881 suppresses the activity of a CEBPB promoter reporter. Loss of C/EBPβ expression prevents growth arrest following androgen deprivation or anti-androgen challenge. Accordingly, suppression of C/EBPβ under low androgen conditions results in reduced expression of senescence-associated secretory genes, significantly decreased number of cells displaying heterochromatin foci and increased numbers of Ki67-positive cells. Ectopic expression of C/EBPβ caused pronounced morphological changes, reduced PC cell growth and increased the number of senescent LNCaP cells. Lastly, we found that senescence contributes to PC cell survival under androgen deprivation, and C/EBPβ-deficient cells were significantly more susceptible to killing by cytotoxic chemotherapy following androgen

  5. Are You Sleep Deprived? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Sleep Disorders Are You Sleep Deprived? Past Issues / Summer 2015 ... ve had enough sleep? You might have a sleep disorder. There are many treatments for sleep disorders and ...

  6. Effects of Nicotine Deprivation on Craving Response Covariation in Smokers

    PubMed Central

    Sayette, Michael A.; Martin, Christopher S.; Hull, Jay G.; Wertz, Joan M.; Perrott, Michael A.

    2009-01-01

    Most models of craving propose that when cravings are strong, diverse responses—thought to index an underlying craving state— covary. Previous studies provided weak support for this hypothesis. The authors tested whether nicotine deprivation affects degree of covariation across multiple measures related to craving. Heavy and light smokers (N = 127) were exposed to smoking cues while either nicotine deprived or nondeprived. Measures included urge ratings, affective valence, a behavioral choice task assessing perceived reinforcement value of smoking, and smoking-related judgment tasks. Results indicated higher correlations in the nicotine-deprived than in nondeprived group. The measures principally responsible for this effect loaded onto a single common Craving factor for nicotine-deprived but not nondeprived smokers. These findings suggest that, under certain conditions, measures of craving-related processes covary. PMID:12653419

  7. Sleep and Nutritional Deprivation and Performance of House Officers.

    ERIC Educational Resources Information Center

    Hawkins, Michael R.; And Others

    1985-01-01

    A study to compare cognitive functioning in acutely and chronically sleep-deprived house officers is described. A multivariate analysis of variance revealed significant deficits in primary mental tasks involving basic rote memory, language, and numeric skills. (Author/MLW)

  8. Family Stability in the Context of Economic Deprivation

    ERIC Educational Resources Information Center

    Odita, Florence C.; Janssens, Mary Ann

    1977-01-01

    This review is aimed at highlighting the impact of economic deprivation on the family, the nucleus of any social system. The low income families receiving "aid for families of the dependent children" (AFDC) are the focus. (Author)

  9. Melatonin improves experimental colitis with sleep deprivation

    PubMed Central

    PARK, YOUNG-SOOK; CHUNG, SOOK-HEE; LEE, SEONG-KYU; KIM, JA-HYUN; KIM, JUN-BONG; KIM, TAE-KYUN; KIM, DONG-SHIN; BAIK, HAING-WOON

    2015-01-01

    Sleep deprivation (SD) is an epidemic phenomenon in modern countries, and its harmful effects are well known. SD acts as an aggravating factor in inflammatory bowel disease. Melatonin is a sleep-related neurohormone, also known to have antioxidant and anti-inflammatory effects in the gastrointestinal tract; however, the effects of melatonin on colitis have been poorly characterized. Thus, in this study, we assessed the measurable effects of SD on experimental colitis and the protective effects of melatonin. For this purpose, male imprinting control region (ICR) mice (n=24) were used; the mice were divided into 4 experimental groups as follows: the control, colitis, colitis with SD and colitis with SD and melatonin groups. Colitis was induced by the administration of 5% dextran sulfate sodium (DSS) in the drinking water for 6 days. The mice were sleep-deprived for 3 days. Changes in body weight, histological analyses of colon tissues and the expression levels of pro-inflammatory cytokines and genes were evaluated. SD aggravated inflammation and these effects were reversed by melatonin in the mice with colitis. In addition, weight loss in the mice with colitis with SD was significantly reduced by the injection of melatonin. Treatment with melatonin led to high survival rates in the mice, in spite of colitis with SD. The levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-17, interferon-γ and tumor necrosis factor-α, in the serum of mice were significantly increased by SD and reduced by melatonin treatment. The melatonin-treated group showed a histological improvement of inflammation. Upon gene analysis, the expression of the inflammatory genes, protein kinase Cζ (PKCζ) and calmodulin 3 (CALM3), was increased by SD, and the levels decreased following treatment with melatonin. The expression levels of the apoptosis-related inducible nitric oxide synthase (iNOS) and wingless-type MMTV integration site family, member 5A (Wnt5a) genes was

  10. Sustained Perceptual Deficits from Transient Sensory Deprivation

    PubMed Central

    Sanes, Dan H.

    2015-01-01

    Sensory pathways display heightened plasticity during development, yet the perceptual consequences of early experience are generally assessed in adulthood. This approach does not allow one to identify transient perceptual changes that may be linked to the central plasticity observed in juvenile animals. Here, we determined whether a brief period of bilateral auditory deprivation affects sound perception in developing and adult gerbils. Animals were reared with bilateral earplugs, either from postnatal day 11 (P11) to postnatal day 23 (P23) (a manipulation previously found to disrupt gerbil cortical properties), or from P23-P35. Fifteen days after earplug removal and restoration of normal thresholds, animals were tested on their ability to detect the presence of amplitude modulation (AM), a temporal cue that supports vocal communication. Animals reared with earplugs from P11-P23 displayed elevated AM detection thresholds, compared with age-matched controls. In contrast, an identical period of earplug rearing at a later age (P23-P35) did not impair auditory perception. Although the AM thresholds of earplug-reared juveniles improved during a week of repeated testing, a subset of juveniles continued to display a perceptual deficit. Furthermore, although the perceptual deficits induced by transient earplug rearing had resolved for most animals by adulthood, a subset of adults displayed impaired performance. Control experiments indicated that earplugging did not disrupt the integrity of the auditory periphery. Together, our results suggest that P11-P23 encompasses a critical period during which sensory deprivation disrupts central mechanisms that support auditory perceptual skills. SIGNIFICANCE STATEMENT Sensory systems are particularly malleable during development. This heightened degree of plasticity is beneficial because it enables the acquisition of complex skills, such as music or language. However, this plasticity comes with a cost: nervous system development

  11. Androgen deprivation-induced NCoA2 promotes metastatic and castration-resistant prostate cancer.

    PubMed

    Qin, Jun; Lee, Hui-Ju; Wu, San-Pin; Lin, Shih-Chieh; Lanz, Rainer B; Creighton, Chad J; DeMayo, Francesco J; Tsai, Sophia Y; Tsai, Ming-Jer

    2014-11-01

    A major clinical hurdle for the management of advanced prostate cancer (PCa) in patients is the resistance of tumors to androgen deprivation therapy (ADT) and their subsequent development into castration-resistant prostate cancer (CRPC). While recent studies have identified potential pathways involved in CRPC development, the drivers of CRPC remain largely undefined. Here we determined that nuclear receptor coactivator 2 (NCoA2, also known as SRC-2), which is frequently amplified or overexpressed in patients with metastatic PCa, mediates development of CRPC. In a murine model, overexpression of NCoA2 in the prostate epithelium resulted in neoplasia and, in combination with Pten deletion, promoted the development of metastasis-prone cancer. Moreover, depletion of NCoA2 in PTEN-deficient mice prevented the development of CRPC. In human androgen-sensitive prostate cancer cells, androgen signaling suppressed NCoA2 expression, and NCoA2 overexpression in murine prostate tumors resulted in hyperactivation of PI3K/AKT and MAPK signaling, promoting tumor malignance. Analysis of PCa patient samples revealed a strong correlation among NCoA2-mediated signaling, disease progression, and PCa recurrence. Taken together, our findings indicate that androgen deprivation induces NCoA2, which in turn mediates activation of PI3K signaling and promotes PCa metastasis and CRPC development. Moreover, these results suggest that the inhibition of NCoA2 has potential for PCa therapy. PMID:25295534

  12. Effects of oxygen deprivation on incubated rat soleus muscle

    NASA Technical Reports Server (NTRS)

    Fagan, Julie M.; Tischler, Marc E.

    1989-01-01

    Isolated soleus muscle deprived of oxygen produces more lactate and alanine than oxygen-supplied muscle. Oxygenated muscle synthesized glutamine, while anoxic muscle used this amino acid. Oxygen deprivation decreased adenine nucleotides leading to the efflux of nucleosides. Protein synthesis and degradation responded differently to anoxia. Synthesis almost completely ceased, while proteolysis increased. Therefore, protein degradation in soleus muscle is enhanced when energy supplies and oxygen tension are low.

  13. Sleep Deprivation and Time-Based Prospective Memory

    PubMed Central

    Esposito, Maria José; Occhionero, Miranda; Cicogna, PierCarla

    2015-01-01

    Study Objectives: To evaluate the effect of sleep deprivation on time-based prospective memory performance, that is, realizing delayed intentions at an appropriate time in the future (e.g., to take a medicine in 30 minutes). Design: Between-subjects experimental design. The experimental group underwent 24 h of total sleep deprivation, and the control group had a regular sleep-wake cycle. Participants were tested at 08:00. Settings: Laboratory. Participants: Fifty healthy young adults (mean age 22 ± 2.1, 31 female). Interventions: 24 h of total sleep deprivation. Measurements and Results: Participants were monitored by wrist actigraphy for 3 days before the experimental session. The following cognitive tasks were administered: one time-based prospective memory task and 3 reasoning tasks as ongoing activity. Objective and subjective vigilance was assessed by the psychomotor vigilance task and a visual analog scale, respectively. To measure the time-based prospective memory task we assessed compliance and clock checking behavior (time monitoring). Sleep deprivation negatively affected time-based prospective memory compliance (P < 0.001), objective vigilance (mean RT: P < 0.001; slowest 10% RT: P < 0.001; lapses: P < 0.005), and subjective vigilance (P < 0.0001). Performance on reasoning tasks and time monitoring behavior did not differ between groups. Conclusions: The results highlight the potential dangerous effects of total sleep deprivation on human behavior, particularly the ability to perform an intended action after a few minutes. Sleep deprivation strongly compromises time-based prospective memory compliance but does not affect time check frequency. Sleep deprivation may impair the mechanism that allows the integration of information related to time monitoring with the prospective intention. Citation: Esposito MJ, Occhionero M, Cicogna P. Sleep deprivation and time-based prospective memory. SLEEP 2015;38(11):1823–1826. PMID:26085303

  14. Vascular Compliance Limits during Sleep Deprivation and Recovery Sleep

    PubMed Central

    Phillips, Derrick J.; Schei, Jennifer L.; Rector, David M.

    2013-01-01

    Study Objectives: Our previous studies showed that evoked hemodynamic responses are smaller during wake compared to sleep; suggesting neural activity is associated with vascular expansion and decreased compliance. We explored whether prolonged activity during sleep deprivation may exacerbate vascular expansion and blunt hemodynamic responses. Design: Evoked auditory responses were generated with periodic 65dB speaker clicks over a 72-h period and measured with cortical electrodes. Evoked hemodynamic responses were measured simultaneously with optical techniques using three light-emitting diodes, and a photodiode. Setting: Animals were housed in separate 30×30×80cm enclosures, tethered to a commutator system and maintained on a 12-h light/dark cycle. Food and water were available ad libitum. Patients or Participants: Seven adult female Sprague-Dawley rats. Interventions: Following a 24-h baseline recording, sleep deprivation was initiated for 0 to 10 h by gentle handling, followed by a 24-h recovery sleep recording. Evoked electrical and hemodynamic responses were measured before, during, and after sleep deprivation. Measurements and Results: Following deprivation, evoked hemodynamic amplitudes were blunted. Steady-state oxyhemoglobin concentration increased during deprivation and remained high during the initial recovery period before returning to baseline levels after approximately 9-h. Conclusions: Sleep deprivation resulted in blood vessel expansion and decreased compliance while lower basal neural activity during recovery sleep may allow blood vessel compliance to recover. Chronic sleep restriction or sleep deprivation could push the vasculature to critical levels, limiting blood delivery, and leading to metabolic deficits with the potential for neural trauma. Citation: Phillips DJ; Schei JL; Rector DM. Vascular compliance limits during sleep deprivation and recovery sleep. SLEEP 2013;36(10):1459-1470. PMID:24082305

  15. Reduced visual processing capacity in sleep deprived persons.

    PubMed

    Kong, Danyang; Soon, Chun Siong; Chee, Michael W L

    2011-03-15

    Multiple experiments have found sleep deprivation to lower task-related parietal and extrastriate visual activation, suggesting a reduction of visual processing capacity in this state. The perceptual load theory of attention (Lavie, 1995) predicts that our capacity to process unattended distractors will be reduced by increasing perceptual difficulty of task-relevant stimuli. Here, we evaluated the effects of sleep deprivation and perceptual load on visual processing capacity by measuring neural repetition-suppression to unattended scenes while healthy volunteers attended to faces embedded in face-scene pictures. Perceptual load did not affect repetition suppression after a normal night of sleep. Sleep deprivation reduced repetition suppression in the parahippocampal place area (PPA) in the high but not low perceptual load condition. Additionally, the extent to which task-related fusiform face area (FFA) activation was reduced after sleep deprivation correlated with behavioral performance and lowered repetition suppression in the PPA. The findings concerning correct responses indicate that a portion of stimulus related activation following a normal night of sleep contributes to potentially useful visual processing capacity that is attenuated following sleep deprivation. Finally, when unattended stimuli are not highly intrusive, sleep deprivation does not appear to increase distractibility. PMID:21195190

  16. Sleep deprivation in adolescents and adults: changes in affect.

    PubMed

    Talbot, Lisa S; McGlinchey, Eleanor L; Kaplan, Katherine A; Dahl, Ronald E; Harvey, Allison G

    2010-12-01

    The present study investigated the impact of sleep deprivation on several aspects of affective functioning in healthy participants selected from three different developmental periods: early adolescence (ages 10-13), midadolescence (ages 13-16), and adulthood (ages 30-60). Participants completed an affective functioning battery under conditions of sleep deprivation (a maximum of 6.5 hours total sleep time on the first night followed by a maximum of 2 hours total sleep time on the second night) and rest (approximately 7-8 hours total sleep time each night for two consecutive nights). Less positive affect was observed in the sleep-deprived, compared to rested, condition. This effect held for 9 of the 12 positive affect items on the PANAS-C. Participants also reported a greater increase in anxiety during a catastrophizing task and rated the likelihood of potential catastrophes as higher when sleep deprived, relative to when rested. Early adolescents appraised their main worry as more threatening when sleep deprived, relative to when rested. These results support and extend previous research underscoring the adverse affective consequences of sleep deprivation. PMID:21058849

  17. Selective REM Sleep Deprivation Improves Expectation-Related Placebo Analgesia

    PubMed Central

    Chouchou, Florian; Chauny, Jean-Marc; Rainville, Pierre; Lavigne, Gilles J.

    2015-01-01

    The placebo effect is a neurobiological and psychophysiological process known to influence perceived pain relief. Optimization of placebo analgesia may contribute to the clinical efficacy and effectiveness of medication for acute and chronic pain management. We know that the placebo effect operates through two main mechanisms, expectations and learning, which is also influenced by sleep. Moreover, a recent study suggested that rapid eye movement (REM) sleep is associated with modulation of expectation-mediated placebo analgesia. We examined placebo analgesia following pharmacological REM sleep deprivation and we tested the hypothesis that relief expectations and placebo analgesia would be improved by experimental REM sleep deprivation in healthy volunteers. Following an adaptive night in a sleep laboratory, 26 healthy volunteers underwent classical experimental placebo analgesic conditioning in the evening combined with pharmacological REM sleep deprivation (clonidine: 13 volunteers or inert control pill: 13 volunteers). Medication was administered in a double-blind manner at bedtime, and placebo analgesia was tested in the morning. Results revealed that 1) placebo analgesia improved with REM sleep deprivation; 2) pain relief expectations did not differ between REM sleep deprivation and control groups; and 3) REM sleep moderated the relationship between pain relief expectations and placebo analgesia. These results support the putative role of REM sleep in modulating placebo analgesia. The mechanisms involved in these improvements in placebo analgesia and pain relief following selective REM sleep deprivation should be further investigated. PMID:26678391

  18. Caffeine withdrawal symptoms and self-administration following caffeine deprivation.

    PubMed

    Mitchell, S H; de Wit, H; Zacny, J P

    1995-08-01

    This study examined the effects of complete or partial caffeine deprivation on withdrawal symptomatology and self-administration of coffee in caffeine-dependent coffee drinkers. Nine habitual coffee drinkers abstained from dietary sources of caffeine for 33.5 h. Caffeine deprivation was manipulated by administering capsules containing 0%, 50%, or 100% of each subject's daily caffeine intake (complete, partial, and no deprivation conditions). Caffeine withdrawal symptomatology was measured using self-report questionnaires. Caffeine self-administration was measured using: i) the amount of coffee subjects earned on a series of concurrent random-ratio schedules that yielded coffee and money reinforcers; ii) the amount of earned coffee they consumed. Saliva samples revealed that subjects complied with the caffeine abstinence instructions. Caffeine withdrawal symptoms occurred reliably following complete caffeine deprivation, though not in the partial deprivation condition. Caffeine self-administration was not related to deprivation condition. We conclude that caffeine withdrawal symptomatology is not necessarily associated with increased caffeine consumption. PMID:7675881

  19. Depression, neighborhood deprivation and risk of type 2 diabetes

    PubMed Central

    Mezuk, Briana; Chaikiat, Åsa; Li, Xinjun; Sundquist, Jan; Kendler, Kenneth S.; Sundquist, Kristina

    2013-01-01

    Neighborhood characteristics have been associated with both depression and diabetes, but to date little attention has been paid to whether the association between depression and diabetes varies across different types of neighborhoods. This prospective study examined the relationship between depression, neighborhood deprivation, and risk of type 2 diabetes among 336,340 adults from a national-representative sample of primary care centers in Sweden (2001–2007). Multi-level logistic regression models were used to assess associations between depression and risk of type 2 diabetes across affluent and deprived neighborhoods. After accounting for demographic, individual-level socioeconomic, and health characteristics, depression was significantly associated with risk of diabetes (odds ratio (OR): 1.10, 95% confidence interval (CI): 1.06–1.14), as was neighborhood deprivation (OR for high vs. low deprivation: 1.66, 95% CI: 1.22–1.34). The interaction term between depression and neighborhood deprivation was non-significant, indicating that the relationship between depression and diabetes risk is similar across levels of neighborhood socioeconomic deprivation. PMID:23771166

  20. Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

    PubMed Central

    Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

    2015-01-01

    Background Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Methods Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. Results During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Conclusions Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness. PMID:26241047

  1. Predicting Psychotic-Like Experiences during Sensory Deprivation

    PubMed Central

    Daniel, Christina; Mason, Oliver J.

    2015-01-01

    Aims. This study aimed to establish the contribution of hallucination proneness, anxiety, suggestibility, and fantasy proneness to psychotic-like experiences (PLEs) reported during brief sensory deprivation. Method. Twenty-four high and 22 low hallucination-prone participants reported on PLEs occurring during brief sensory deprivation and at baseline. State/trait anxiety, suggestibility, and fantasy proneness were also measured. Results. Both groups experienced a significant increase in PLEs in sensory deprivation. The high hallucination prone group reported more PLEs both at baseline and in sensory deprivation. They also scored significantly higher on measures of state/trait anxiety, suggestibility, and fantasy proneness, though these did not explain the effects of group or condition. Regression analysis found hallucination proneness to be the best predictor of the increase in PLEs, with state anxiety also being a significant predictor. Fantasy proneness and suggestibility were not significant predictors. Conclusion. This study suggests the increase in PLEs reported during sensory deprivation reflects a genuine aberration in perceptual experience, as opposed to increased tendency to make false reports due to suggestibility of fantasy proneness. The study provides further support for the use of sensory deprivation as a safe and effective nonpharmacological model of psychosis. PMID:25811027

  2. Sleep deprivation due to shift work.

    PubMed

    Costa, Giovanni

    2015-01-01

    Sleep deprivation due to shift work is related to perturbation of the sleep/wake cycle, associated with the modified activity/rest pattern. This may cause a significant disruption of circadian rhythms of biologic functions, driven by the body clock located in the suprachiasmatic nuclei of the hypothalamus. Shift and night workers have to change sleep times and strategies according to their duty periods; consequently, both sleep length and quality can be considerably affected depending on the variable start and finish times on different shifts. About 10% of night and rotating shift workers, aged between 18 and 65 years, have been estimated to have a diagnosable "shift-work sleep disorder," according to the International Classification of Sleep Disorders, version 2 (ICSD-2). In the long run, this may lead to persistent and severe disturbances of sleep, chronic fatigue and psychoneurotic syndromes, besides being a risk or aggravating factor for accidents, gastrointestinal, cardiovascular, and reproductive disorders, as well as, probably, for cancer. Preventive and corrective actions deal with the organization of shift schedules according to ergonomic criteria, careful health surveillance, appropriate education and training on effective countermeasures, in particular, sleep hygiene and napping. PMID:26563802

  3. Serine deprivation enhances antineoplastic activity of biguanides.

    PubMed

    Gravel, Simon-Pierre; Hulea, Laura; Toban, Nader; Birman, Elena; Blouin, Marie-José; Zakikhani, Mahvash; Zhao, Yunhua; Topisirovic, Ivan; St-Pierre, Julie; Pollak, Michael

    2014-12-15

    Metformin, a biguanide widely used in the treatment of type II diabetes, clearly exhibits antineoplastic activity in experimental models and has been reported to reduce cancer incidence in diabetics. There are ongoing clinical trials to evaluate its antitumor properties, which may relate to its fundamental activity as an inhibitor of oxidative phosphorylation. Here, we show that serine withdrawal increases the antineoplastic effects of phenformin (a potent biguanide structurally related to metformin). Serine synthesis was not inhibited by biguanides. Instead, metabolic studies indicated a requirement for serine to allow cells to compensate for biguanide-induced decrease in oxidative phosphorylation by upregulating glycolysis. Furthermore, serine deprivation modified the impact of metformin on the relative abundance of metabolites within the citric acid cycle. In mice, a serine-deficient diet reduced serine levels in tumors and significantly enhanced the tumor growth-inhibitory actions of biguanide treatment. Our results define a dietary manipulation that can enhance the efficacy of biguanides as antineoplastic agents that target cancer cell energy metabolism. PMID:25377470

  4. Circadian Rhythms, Sleep Deprivation, and Human Performance

    PubMed Central

    Goel, Namni; Basner, Mathias; Rao, Hengyi; Dinges, David F.

    2014-01-01

    Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep–wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance. Endogenous circadian rhythms in neurobehavioral functions, including physiological alertness and cognitive performance, have been demonstrated using special laboratory protocols that reveal the interaction of the biological clock with the sleep homeostatic drive. Individual differences in circadian rhythms and genetic and other components underlying such differences also influence waking neurobehavioral functions. Both acute total sleep deprivation and chronic sleep restriction increase homeostatic sleep drive and degrade waking neurobehavioral functions as reflected in sleepiness, attention, cognitive speed, and memory. Recent evidence indicating a high degree of stability in neurobehavioral responses to sleep loss suggests that these trait-like individual differences are phenotypic and likely involve genetic components, including circadian genes. Recent experiments have revealed both sleep homeostatic and circadian effects on brain metabolism and neural activation. Investigation of the neural and genetic mechanisms underlying the dynamically complex interaction between sleep homeostasis and circadian systems is beginning. A key goal of this work is to identify biomarkers that accurately predict human performance in situations in which the circadian and sleep homeostatic systems are perturbed. PMID:23899598

  5. Determinants of smoking-induced deprivation in China

    PubMed Central

    Yao, Tingting; Huang, Jidong; Sung, Hai-Yen; Ong, Michael K; Mao, Zhengzhong; Jiang, Yuan; Fong, Geoffrey T; Max, Wendy

    2015-01-01

    Objective Spending on cigarettes may deprive households of other items like food. The goal of this study was to examine the prevalence of and factors associated with this smoking-induced deprivation among adult smokers in China. Methods The data came from waves 1–3 of the International Tobacco Control (ITC) China Survey, conducted from 2006 to 2009 among urban adults aged 18 years or older in China. We focus on the samples of current smokers from six cities (N=7981). Smoking-induced deprivation was measured with the survey question, “In the last six months, have you spent money on cigarettes that you knew would be better spent on household essentials like food?” We examined whether sociodemographic factors, smoking intensity and price paid per pack of cigarettes were associated with smoking-induced deprivation using generalised estimating equations modelling. Findings 7.3% of smokers reported smoking-induced deprivation due to purchasing cigarettes. Low-income and middle-income smokers were more likely to have smoking-induced deprivation compared with high-income smokers (adjusted OR (AOR)=2.06, 95% CI 1.32 to 2.31; AOR=1.44, 95% CI 1.10 to 1.69); smokers living in Shenyang (AOR=1.68, 95% CI 1.25 to 2.24) and Yinchuan (AOR=2.50, 95% CI 1.89 to 3.32) were more likely to have smoking-induced deprivation compared with smokers living in Beijing. Retired smokers were less likely to have smoking-induced deprivation compared with employed smokers (AOR=0.67, 95% CI 0.52 to 0.87). There was no statistically significant relationship between smoking intensity, price paid per pack of cigarettes and smoking-induced deprivation. Conclusions Our findings indicate that certain groups of smokers in China acknowledge spending money on cigarettes that could be better spent on household essentials. Tobacco control policies that reduce smoking in China may improve household living standards by reducing smoking-induced deprivation. PMID:24827978

  6. Impact of Acute Sleep Deprivation on Sarcasm Detection

    PubMed Central

    Mary, Alison; Slama, Hichem; Cleeremans, Axel; Peigneux, Philippe; Kissine, Mikhail

    2015-01-01

    There is growing evidence that sleep plays a pivotal role on health, cognition and emotional regulation. However, the interplay between sleep and social cognition remains an uncharted research area. In particular, little is known about the impact of sleep deprivation on sarcasm detection, an ability which, once altered, may hamper everyday social interactions. The aim of this study is to determine whether sleep-deprived participants are as able as sleep-rested participants to adopt another perspective in gauging sarcastic statements. At 9am, after a whole night of sleep (n = 15) or a sleep deprivation night (n = 15), participants had to read the description of an event happening to a group of friends. An ambiguous voicemail message left by one of the friends on another's phone was then presented, and participants had to decide whether the recipient would perceive the message as sincere or as sarcastic. Messages were uttered with a neutral intonation and were either: (1) sarcastic from both the participant’s and the addressee’s perspectives (i.e. both had access to the relevant background knowledge to gauge the message as sarcastic), (2) sarcastic from the participant’s but not from the addressee’s perspective (i.e. the addressee lacked context knowledge to detect sarcasm) or (3) sincere. A fourth category consisted in messages sarcastic from both the participant’s and from the addressee’s perspective, uttered with a sarcastic tone. Although sleep-deprived participants were as accurate as sleep-rested participants in interpreting the voice message, they were also slower. Blunted reaction time was not fully explained by generalized cognitive slowing after sleep deprivation; rather, it could reflect a compensatory mechanism supporting normative accuracy level in sarcasm understanding. Introducing prosodic cues compensated for increased processing difficulties in sarcasm detection after sleep deprivation. Our findings support the hypothesis that sleep

  7. BRAF inhibitor resistance enhances vulnerability to arginine deprivation in melanoma

    PubMed Central

    Li, Ying-Ying; Wu, Chunjing; Chen, Shu-Mei; Shah, Sumedh S.; Wangpaichitr, Medhi; Feun, Lynn G.; Kuo, Macus T.; Suarez, Miguel; Prince, Jeffrey; Savaraj, Niramol

    2016-01-01

    BRAF inhibitor (BRAFi) has been used for treatment of melanomas harboring V600E mutation. Despite a high initial response rate, resistance to BRAFi is inevitable. Here, we demonstrate that BRAFi-resistant (BR) melanomas are susceptible to arginine deprivation due to inability to initiate re-expression of argininosuccinate synthetase (ASS1, a key enzyme for arginine synthesis) as well as ineffective autophagy. Autophagy and ASS1 re-expression are known to protect melanoma cells from cell death upon arginine deprivation. When melanoma cells become BR cells by long-term in vitro incubation with BRAFi, c-Myc-mediated ASS1 re-expression and the levels of autophagy-associated proteins (AMPK-α1 and Atg5) are attenuated. Furthermore, our study uncovers that downregulation of deubiquitinase USP28 which results in more active c-Myc degradation via ubiquitin-proteasome machinery is the primary mechanism for inability to re-express ASS1 upon arginine deprivation in BR cells. Overexpression of USP28 in BR cells enhances c-Myc expression and hence increases ASS1 transcription upon arginine deprivation, and consequently leads to cell survival. On the other hand, overexpression of Atg5 or AMPK-α1 in BR cells can redirect arginine deprivation-induced apoptosis toward autophagy. The xenograft models also confirm that BR tumors possess lower expression of ASS1 and are hypersensitive to arginine deprivation. These biochemical changes in BRAFi resistance which make them vulnerable to arginine deprivation can be exploited for the future treatment of BR melanoma patients. PMID:26771234

  8. Impact of Acute Sleep Deprivation on Sarcasm Detection.

    PubMed

    Deliens, Gaétane; Stercq, Fanny; Mary, Alison; Slama, Hichem; Cleeremans, Axel; Peigneux, Philippe; Kissine, Mikhail

    2015-01-01

    There is growing evidence that sleep plays a pivotal role on health, cognition and emotional regulation. However, the interplay between sleep and social cognition remains an uncharted research area. In particular, little is known about the impact of sleep deprivation on sarcasm detection, an ability which, once altered, may hamper everyday social interactions. The aim of this study is to determine whether sleep-deprived participants are as able as sleep-rested participants to adopt another perspective in gauging sarcastic statements. At 9am, after a whole night of sleep (n = 15) or a sleep deprivation night (n = 15), participants had to read the description of an event happening to a group of friends. An ambiguous voicemail message left by one of the friends on another's phone was then presented, and participants had to decide whether the recipient would perceive the message as sincere or as sarcastic. Messages were uttered with a neutral intonation and were either: (1) sarcastic from both the participant's and the addressee's perspectives (i.e. both had access to the relevant background knowledge to gauge the message as sarcastic), (2) sarcastic from the participant's but not from the addressee's perspective (i.e. the addressee lacked context knowledge to detect sarcasm) or (3) sincere. A fourth category consisted in messages sarcastic from both the participant's and from the addressee's perspective, uttered with a sarcastic tone. Although sleep-deprived participants were as accurate as sleep-rested participants in interpreting the voice message, they were also slower. Blunted reaction time was not fully explained by generalized cognitive slowing after sleep deprivation; rather, it could reflect a compensatory mechanism supporting normative accuracy level in sarcasm understanding. Introducing prosodic cues compensated for increased processing difficulties in sarcasm detection after sleep deprivation. Our findings support the hypothesis that sleep deprivation might

  9. The effect of dietary pyridoxine on arsenic deprivation in rats

    SciTech Connect

    Uthus, E.O.; Poelllot, R. )

    1991-03-15

    In experiments on As deprivation, many findings indicate that As can affect enzymes or metabolites that are also influenced by vitamin B{sub 6}. Thus, an experiment was designed to ascertain the effect of pyridoxine (pyr) on As deprivation in rats. Male, weanling rats were fed an amino acid based diet containing 0.24% methionine (M) and less than 15 ng As/g. Dietary variables were As, 0 or 1 {mu}g/g; M, 0 or 3 g/kg; and pyridoxine, 0 or 10 mg/kg. After 10 weeks, growth was reduced by As, Pyr, or M deprivation. Both endogenous ({minus}PP) and pyridoxal phosphate-stimulated (+PP) RBC aspartate aminotransferase were decreased by Pyr deficiency. The ratio of +PP/{minus}PP, known as the activation coefficient (AC), was affected by an interaction between As and Pyr. Pyr deficiency resulted in a less marked increase in AC in the As-deprived rats than in the As-supplemented rats. Plasma Fe was slightly decreased by Pyr deficiency in the As-deprived rats but increased by Pyr deficiency in the As-supplemented rats. Plasma threonine and serine were increased by As supplementation in the Pyr-deficient rats but there was no effect of As supplementation in the Pyr-supplemented rats. Plasma alanine was decreased by As or Pyr deprivation. In Pyr deficiency, As deprivation had no effect on plasma glycine (G) in the M-deficient rats but decreased G in the M-supplemented rats. In the Pyr-supplemented rats, As had no effect on G, regardless of M. The findings indicate that As and Pyr interact to affect amino acid metabolism.

  10. Cellular consequences of sleep deprivation in the brain.

    PubMed

    Cirelli, Chiara

    2006-10-01

    Several recent studies have used transcriptomics approaches to characterize the molecular correlates of sleep, waking, and sleep deprivation. This analysis may help in understanding the benefits that sleep brings to the brain at the cellular level. The studies are still limited in number and focus on a few brain regions, but some consistent findings are emerging. Sleep, spontaneous wakefulness, short-term, and long-term sleep deprivation are each associated with the upregulation of hundreds of genes in the cerebral cortex and other brain areas. In fruit flies as well as in mammals, three categories of genes are consistently upregulated during waking and short-term sleep deprivation relative to sleep. They include genes involved in energy metabolism, synaptic potentiation, and the response to cellular stress. In the rat cerebral cortex, transcriptional changes associated with prolonged sleep loss differ significantly from those observed during short-term sleep deprivation. However, it is too early to draw firm conclusions relative to the molecular consequences of sleep deprivation, and more extensive studies using DNA and protein arrays are needed in different species and in different brain regions. PMID:16920372

  11. Physiological responses of Yellowstone bison to winter nutritional deprivation

    USGS Publications Warehouse

    DelGiudice, Glenn D.; Singer, Francis J.; Seal, Ulysses S.; Bowser, Gillian

    1994-01-01

    Because nutrition is critically related to other aspects of bison (Bison bison) ecology, and the winter ranges inhabited by bison in Yellowstone National Park (YNP) are ecologically diverse, it was important to determine if nutritional deprivation differences occurred among winter ranges. We used chemistry profiles of urine suspended in snow to compare nutritional deprivation of bison from January to April 1988 on 4 sampling areas of 3 winter ranges in YNP. Declining (P < 0.001) trends of urinary potassium: creatinine ratios in bison on all 4 sampling areas indicated progressive nutritional deprivation through late March. Concurrent increases (P ≤ 0.001) in mean urea nitrogen: creatinine ratios from late February through late march in 3 of 4 areas suggested that increased net catabolism was occurring. Diminished creatinine ratios of sodium and phosphorus reflected low dietary intake of these minerals throughout winter. Mean values and trends of urinary characteristics indicated nutritional deprivation varied among 3 winter ranges in YNP. Continued physiological monitoring of nutritional deprivation, along with detailed examination of other aspects of the bison's ecology, will provide greater insight into the role of ungulate nutrition in the dynamics of such a complex system and improve management.

  12. Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula

    PubMed Central

    Gao, Yanxia

    2016-01-01

    Sleep is governed by homeostasis and the circadian clock. Clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. The lateral habenular nucleus (LHb) has been implicated in sleep-wake regulation, since LHb gene expression demonstrates circadian oscillation characteristics. This study focuses on the participation of LHb clock genes in regulating sleep homeostasis, as the nature of their involvement is unclear. In this study, we observed changes in sleep pattern following sleep deprivation in LHb-lesioned rats using EEG recording techniques. And then the changes of clock gene expression (Per1, Per2, and Bmal1) in the LHb after 6 hours of sleep deprivation were detected by using real-time quantitative PCR (qPCR). We found that sleep deprivation increased the length of Non-Rapid Eye Movement Sleep (NREMS) and decreased wakefulness. LHb-lesioning decreased the amplitude of reduced wake time and increased NREMS following sleep deprivation in rats. qPCR results demonstrated that Per2 expression was elevated after sleep deprivation, while the other two genes were unaffected. Following sleep recovery, Per2 expression was comparable to the control group. This study provides the basis for further research on the role of LHb Per2 gene in the regulation of sleep homeostasis. PMID:27413249

  13. Sleep deprivation affects extinction but not acquisition memory in honeybees.

    PubMed

    Hussaini, Syed Abid; Bogusch, Lisa; Landgraf, Tim; Menzel, Randolf

    2009-11-01

    Sleep-like behavior has been studied in honeybees before, but the relationship between sleep and memory formation has not been explored. Here we describe a new approach to address the question if sleep in bees, like in other animals, improves memory consolidation. Restrained bees were observed by a web camera, and their antennal activities were used as indicators of sleep. We found that the bees sleep more during the dark phase of the day compared with the light phase. Sleep phases were characterized by two distinct patterns of antennal activities: symmetrical activity, more prominent during the dark phase; and asymmetrical activity, more common during the light phase. Sleep-deprived bees showed rebound the following day, confirming effective deprivation of sleep. After appetitive conditioning of the bees to various olfactory stimuli, we observed their sleep. Bees conditioned to odor with sugar reward showed lesser sleep compared with bees that were exposed to either reward alone or air alone. Next, we asked whether sleep deprivation affects memory consolidation. While sleep deprivation had no effect on retention scores after odor acquisition, retention for extinction learning was significantly reduced, indicating that consolidation of extinction memory but not acquisition memory was affected by sleep deprivation. PMID:19864296

  14. Sleep Deprivation Influences Circadian Gene Expression in the Lateral Habenula.

    PubMed

    Zhang, Beilin; Gao, Yanxia; Li, Yang; Yang, Jing; Zhao, Hua

    2016-01-01

    Sleep is governed by homeostasis and the circadian clock. Clock genes play an important role in the generation and maintenance of circadian rhythms but are also involved in regulating sleep homeostasis. The lateral habenular nucleus (LHb) has been implicated in sleep-wake regulation, since LHb gene expression demonstrates circadian oscillation characteristics. This study focuses on the participation of LHb clock genes in regulating sleep homeostasis, as the nature of their involvement is unclear. In this study, we observed changes in sleep pattern following sleep deprivation in LHb-lesioned rats using EEG recording techniques. And then the changes of clock gene expression (Per1, Per2, and Bmal1) in the LHb after 6 hours of sleep deprivation were detected by using real-time quantitative PCR (qPCR). We found that sleep deprivation increased the length of Non-Rapid Eye Movement Sleep (NREMS) and decreased wakefulness. LHb-lesioning decreased the amplitude of reduced wake time and increased NREMS following sleep deprivation in rats. qPCR results demonstrated that Per2 expression was elevated after sleep deprivation, while the other two genes were unaffected. Following sleep recovery, Per2 expression was comparable to the control group. This study provides the basis for further research on the role of LHb Per2 gene in the regulation of sleep homeostasis. PMID:27413249

  15. Relative deprivation and risk factors for obesity in Canadian adolescents

    PubMed Central

    Elgar, Frank J.; Xie, Annie; Pförtner, Timo-Kolja; White, James; Pickett, Kate E.

    2016-01-01

    Research on socioeconomic differences in overweight and obesity and on the ecological association between income inequality and obesity prevalence suggests that relative deprivation may contribute to lifestyle risk factors for obesity independently of absolute affluence. We tested this hypothesis using data on 25,980 adolescents (11–15 years) in the 2010 Canadian Health Behaviour in School-aged Children (HBSC) study. The Yitzhaki index of relative deprivation was applied to the HBSC Family Affluence Scale, an index of common material assets, with more affluent schoolmates representing the comparative reference group. Regression analysis tested the associations between relative deprivation and four obesity risk factors (skipping breakfasts, physical activity, and healthful and unhealthful food choices) plus dietary restraint. Relative deprivation uniquely related to skipping breakfasts, less physical activity, fewer healthful food choices (e.g., fruits, vegetables, whole grain breads), and a lower likelihood of dieting to lose weight. Consistent with Runciman's (1966) theory of relative deprivation and with psychosocial interpretations of the health consequences of income inequality, the results indicate that having mostly better off schoolmates can contribute to poorer health behaviours independently of school-level affluence and subjective social status. We discuss the implications of these findings for understanding the social origins of obesity and targeting health interventions. PMID:26851410

  16. Relative deprivation and risk factors for obesity in Canadian adolescents.

    PubMed

    Elgar, Frank J; Xie, Annie; Pförtner, Timo-Kolja; White, James; Pickett, Kate E

    2016-03-01

    Research on socioeconomic differences in overweight and obesity and on the ecological association between income inequality and obesity prevalence suggests that relative deprivation may contribute to lifestyle risk factors for obesity independently of absolute affluence. We tested this hypothesis using data on 25,980 adolescents (11-15 years) in the 2010 Canadian Health Behaviour in School-aged Children (HBSC) study. The Yitzhaki index of relative deprivation was applied to the HBSC Family Affluence Scale, an index of common material assets, with more affluent schoolmates representing the comparative reference group. Regression analysis tested the associations between relative deprivation and four obesity risk factors (skipping breakfasts, physical activity, and healthful and unhealthful food choices) plus dietary restraint. Relative deprivation uniquely related to skipping breakfasts, less physical activity, fewer healthful food choices (e.g., fruits, vegetables, whole grain breads), and a lower likelihood of dieting to lose weight. Consistent with Runciman's (1966) theory of relative deprivation and with psychosocial interpretations of the health consequences of income inequality, the results indicate that having mostly better off schoolmates can contribute to poorer health behaviours independently of school-level affluence and subjective social status. We discuss the implications of these findings for understanding the social origins of obesity and targeting health interventions. PMID:26851410

  17. Violence and Touch Deprivation in Adolescents.

    ERIC Educational Resources Information Center

    Field, Tiffany

    2002-01-01

    Children and adolescents who are diagnosed as conduct disordered and violent have less physically intimate relationships. This may be a factor in the development of their disorder. Physical contact treatments like massage therapy may help reduce their aggressive behavior and normalize their EEG and biochemical profiles. (Contains 79 references.)…

  18. Covert Suicidal Impulses in Maternally Deprived Children.

    ERIC Educational Resources Information Center

    Kliman, Gilbert; Lubin, Harriet

    This paper discusses the development of suicidal impulses in children who have lost their mothers due to abandonment or death. The paper is based on two psychoanalytic case studies, in which the children were in therapy when the first suicidal impulses emerged. A pattern is described in which bereaved children's intense wishes to have their…

  19. Hormone Therapy Plus Chemotherapy for Metastatic Prostate Cancer

    Cancer.gov

    A trial of androgen deprivation therapy (ADT) plus six cycles of docetaxel versus ADT alone found that after a median follow-up of nearly 29 months, median overall survival was 13.6 months longer with the combination therapy than with ADT alone (57.6vs44

  20. Language Therapy for a Child with Delayed Language Development: A Preliminary Study of Language Therapy Using Sign Language.

    ERIC Educational Resources Information Center

    Wakaba, Yoko Yamaguchi; And Others

    1989-01-01

    A 3-years-and-11-months-old Japanese girl showed delayed language development and emotional disturbance and was believed to suffer from maternal deprivation. A treatment program was developed consisting of three kinds of therapy: (1) nondirective play therapy; (2) language training; and (3) counseling for the mother. The language training involved…

  1. Increased Automaticity and Altered Temporal Preparation Following Sleep Deprivation

    PubMed Central

    Kong, Danyang; Asplund, Christopher L.; Ling, Aiqing; Chee, Michael W.L.

    2015-01-01

    Study Objectives: Temporal expectation enables us to focus limited processing resources, thereby optimizing perceptual and motor processing for critical upcoming events. We investigated the effects of total sleep deprivation (TSD) on temporal expectation by evaluating the foreperiod and sequential effects during a psychomotor vigilance task (PVT). We also examined how these two measures were modulated by vulnerability to TSD. Design: Three 10-min visual PVT sessions using uniformly distributed foreperiods were conducted in the wake-maintenance zone the evening before sleep deprivation (ESD) and three more in the morning following approximately 22 h of TSD. TSD vulnerable and nonvulnerable groups were determined by a tertile split of participants based on the change in the number of behavioral lapses recorded during ESD and TSD. A subset of participants performed six additional 10-min modified auditory PVTs with exponentially distributed foreperiods during rested wakefulness (RW) and TSD to test the effect of temporal distribution on foreperiod and sequential effects. Setting: Sleep laboratory. Participants: There were 172 young healthy participants (90 males) with regular sleep patterns. Nineteen of these participants performed the modified auditory PVT. Measurements and Results: Despite behavioral lapses and slower response times, sleep deprived participants could still perceive the conditional probability of temporal events and modify their level of preparation accordingly. Both foreperiod and sequential effects were magnified following sleep deprivation in vulnerable individuals. Only the foreperiod effect increased in nonvulnerable individuals. Conclusions: The preservation of foreperiod and sequential effects suggests that implicit time perception and temporal preparedness are intact during total sleep deprivation. Individuals appear to reallocate their depleted preparatory resources to more probable event timings in ongoing trials, whereas vulnerable

  2. Sustained attention performance during sleep deprivation: evidence of state instability

    NASA Technical Reports Server (NTRS)

    Doran, S. M.; Van Dongen, H. P.; Dinges, D. F.

    2001-01-01

    Nathaniel Kleitman was the first to observe that sleep deprivation in humans did not eliminate the ability to perform neurobehavioral functions, but it did make it difficult to maintain stable performance for more than a few minutes. To investigate variability in performance as a function of sleep deprivation, n = 13 subjects were tested every 2 hours on a 10-minute, sustained-attention, psychomotor vigilance task (PVT) throughout 88 hours of total sleep deprivation (TSD condition), and compared to a control group of n = 15 subjects who were permitted a 2-hour nap every 12 hours (NAP condition) throughout the 88-hour period. PVT reaction time means and standard deviations increased markedly among subjects and within each individual subject in the TSD condition relative to the NAP condition. TSD subjects also had increasingly greater performance variability as a function of time on task after 18 hours of wakefulness. During sleep deprivation, variability in PVT performance reflected a combination of normal timely responses, errors of omission (i.e., lapses), and errors of commission (i.e., responding when no stimulus was present). Errors of omission and errors of commission were highly intercorrelated across deprivation in the TSD condition (r = 0.85, p = 0.0001), suggesting that performance instability is more likely to include compensatory effort than a lack of motivation. The marked increases in PVT performance variability as sleep loss continued supports the "state instability" hypothesis, which posits that performance during sleep deprivation is increasingly variable due to the influence of sleep initiating mechanisms on the endogenous capacity to maintain attention and alertness, thereby creating an unstable state that fluctuates within seconds and that cannot be characterized as either fully awake or asleep.

  3. The influence of social deprivation on length of hospitalisation.

    PubMed

    Yilmaz, Engin; Raynaud, Denis

    2013-04-01

    The implementation of activity-based payment system named T2A-tarification à l'activité-in 2004 profoundly modified the financing of French hospitals. Presently applied to activities concerning medicine, surgery and obstetrics, the pricing for these activities was developed using the National Costs Study. The considerable differences observed between costs in the private sector and those in the public sector are in part justified, by the latter, by caring for patients with social deprivation. The goal of this study is to measure the influence of social deprivation on the length of hospitalisation. A survey on inpatient social deprivation was carried out from November to December 2008 by the French Ministry of Health (Department of Research, Study, Evaluation and Statistics-DREES, and technical agency of Hospital information-ATIH). Four dimensions of social deprivation were taken into consideration after a previous qualitative study: social isolation, quality of housing, level of income and access to rights. The sample is based on 27 hospitals, including public and private (for-profit and not-for-profit), representing 57,175 stays, 6,800 of which were patients with social deprivation. After multivariate analyses adjusted for age, severity of illness and DRG, we found that there was a longer length of stay for inpatients with social deprivation (+16%), and in particular for patients living in social isolation (+17%) and for patients with inadequate housing (+17%). The impact of low income on the length of stay is less important. However, low income associated with inadequate housing significantly increases lengths of stay (+24%). PMID:22095444

  4. Sleep Deprivation and Circadian Disruption: Stress, Allostasis, and Allostatic Load.

    PubMed

    McEwen, Bruce S; Karatsoreos, Ilia N

    2015-03-01

    Sleep has important homeostatic functions, and circadian rhythms organize physiology and behavior on a daily basis to insure optimal function. Sleep deprivation and circadian disruption can be stressors, enhancers of other stressors that have consequences for the brain and many body systems. Whether the origins of circadian disruption and sleep disruption and deprivation are from anxiety, depression, shift work, long-distance air travel, or a hectic lifestyle, there are consequences that impair brain functions and contribute to the cumulative wear and tear on body systems caused by too much stress and/or inefficient management of the systems that promote adaptation. PMID:26055668

  5. Relationship between Statin Utilization and Socioeconomic Deprivation in Hungary

    PubMed Central

    Boruzs, Klára; Juhász, Attila; Nagy, Csilla; Ádány, Róza; Bíró, Klára

    2016-01-01

    The risk of premature mortality caused by cardiovascular diseases (CVDs) is approximately three times higher in the Central Eastern European region than in high income European countries, which suggests a lack and/or ineffectiveness of preventive interventions against CVDs. The aim of the present study was to provide data on the relationship between premature CVD mortality, statin utilization as a preventive medication and socioeconomic deprivation at the district level in Hungary. As a conceptually new approach, the prescription of statins, the prescription redemption and the ratio between redemption and prescription rates were also investigated. The number of prescriptions for statins and the number of redeemed statin prescriptions were obtained from the National Health Insurance Fund Administration of Hungary for each primary healthcare practice for the entire year of 2012. The data were aggregated at the district level. To define the frequency of prescription and of redemption, the denominator was the number of the 40+-year-old population adjusted by the rates of 60+-year-old population of the district. The standardized mortality rates, frequency of statin prescriptions, redeemed statin prescriptions, and ratios for compliance in relation to the national average were mapped using the “disease mapping” option, and their association with deprivation (tertile of deprivation index as a district-based categorical covariate) was defined using the risk analysis capabilities within the Rapid Inquiry Facility. The risk analysis showed a significant positive association between deprivation and the relative risk of premature cardiovascular mortality, and a reverse J-shaped association between the relative frequency of statin prescriptions and deprivation. Districts with the highest deprivation showed a low relative frequency of statin prescriptions; however, significantly higher primary compliance (redemption) was observed in districts with the highest deprivation

  6. Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

    PubMed Central

    2012-01-01

    Background There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented. Methods/design We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed) on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7–10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over). Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and secondary endpoints will

  7. Subjective relative deprivation is associated with poorer physical and mental health.

    PubMed

    Mishra, Sandeep; Carleton, R Nicholas

    2015-12-01

    Substantial epidemiological evidence has shown that income inequality and objective measures of relative deprivation are associated with poorer health outcomes. However, surprisingly little research has examined whether subjective feelings of relative deprivation are similarly linked with poorer health outcomes. The relative deprivation hypothesis suggests that inequality affects health at the individual level through negative consequences of social comparison. We directly examined the relationship between subjective feelings of personal relative deprivation and self-reported physical and mental health in a diverse community sample (n = 328). Results demonstrated that subjective feelings of personal relative deprivation are associated with significantly poorer physical and mental health. These relationships held even when accounting for covariates that have been previously associated with both relative deprivation and health. These results further support the link between relative deprivation and health outcomes and suggest that addressing root causes of relative deprivation may lead to greater individual health. PMID:26575605

  8. Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation

    PubMed Central

    Ciminale, Vincenzo; Silic-Benussi, Micol; Guzzo, Giulia; Rasola, Andrea; Frasson, Chiara; Nardo, Giorgia; Zulato, Elisabetta; Nicoletto, Maria Ornella; Manicone, Mariangela

    2014-01-01

    We investigated the metabolic profile of cancer stem cells (CSC) isolated from patients with epithelial ovarian cancer. CSC overexpressed genes associated with glucose uptake, oxidative phosphorylation (OXPHOS), and fatty acid β-oxidation, indicating higher ability to direct pyruvate towards the Krebs cycle. Consistent with a metabolic profile dominated by OXPHOS, the CSC showed higher mitochondrial reactive oxygen species (ROS) production and elevated membrane potential, and underwent apoptosis upon inhibition of the mitochondrial respiratory chain. The CSC also had a high rate of pentose phosphate pathway (PPP) activity, which is not typical of cells privileging OXPHOS over glycolysis, and may rather reflect the PPP role in recharging scavenging enzymes. Furthermore, CSC resisted in vitro and in vivo glucose deprivation, while maintaining their CSC phenotype and OXPHOS profile. These observations may explain the CSC resistance to anti-angiogenic therapies, and indicate this peculiar metabolic profile as a possible target of novel treatment strategies. PMID:24946808

  9. Antivascular Effects of Neoadjuvant Androgen Deprivation for Prostate Cancer: An In Vivo Human Study Using Susceptibility and Relaxivity Dynamic MRI

    SciTech Connect

    Alonzi, Roberto; Padhani, Anwar R.; Taylor, N. Jane; Collins, David J.; D'Arcy, James A.; Stirling, J. James; Saunders, Michele I.; Hoskin, Peter J.

    2011-07-01

    Purpose: The antivascular effects of androgen deprivation have been investigated in animal models; however, there has been minimal investigation in human prostate cancer. This study tested the hypothesis that androgen deprivation causes significant reductions in human prostate tumor blood flow and the induction of hypoxia at a magnitude and in a time scale relevant to the neoadjuvant setting before radiotherapy. Methods and Materials: Twenty patients were examined, each with five multi-parameter magnetic resonance imaging scans: two scans before the commencement of androgen suppression, one scan after 1 month of hormone treatment, and two further scans after 3 months of therapy. Quantitative parametric maps of the prostate informing on relative blood flow (rBF), relative blood volume (rBV), vascular permeability (transfer constant [K{sup trans}]), leakage space (v{sub e}) and blood oxygenation (intrinsic relaxivity [R{sub 2}*]) were calculated. Results: Tumor blood volume and blood flow decreased by 83% and 79%, respectively, in the first month (p < 0.0001), with 74% of patients showing significant changes. The proportion of individual patients who achieved significant changes in T1 kinetic parameter values after 3 months of androgen deprivation for tumor measurements was 68% for K{sup trans} and 53% for v{sub e} By 3 months, significant increases in R{sub 2}* had occurred in prostate tumor, with a rise of 41.1% (p < 0.0001). Conclusions: Androgen deprivation induces profound vascular collapse within 1 month of starting treatment. Increased R{sub 2}* in regions of prostate cancer and a decrease in blood volume suggest a reduction in tumor oxygenation.

  10. Socioeconomic deprivation and barriers to live-donor kidney transplantation: a qualitative study of deceased-donor kidney transplant recipients

    PubMed Central

    Bailey, Phillippa K; Ben-Shlomo, Yoav; Tomson, Charles R V; Owen-Smith, Amanda

    2016-01-01

    Objectives Socioeconomically deprived individuals with renal disease are less likely to receive a live-donor kidney transplant than less-deprived individuals. This qualitative study aimed to identify reasons for the observed socioeconomic disparity in live-donor kidney transplantation. Design A qualitative study using face-to-face in-depth semistructured interviews. Setting A UK tertiary renal referral hospital and transplant centre. Participants Purposive sampling was used to select deceased-donor transplant recipients from areas of high socioeconomic deprivation (SED) (19 participants), followed by a low SED comparison group (13 participants), aiming for maximum diversity in terms of age, gender, ethnicity, primary renal disease and previous renal replacement therapy. Methods Participants were interviewed following their routine transplant clinic review. Interviews were digitally audio-recorded and transcribed verbatim. Transcripts were coded using NVivo software and analysed using the constant comparison method described in Grounded Theory. Results Themes common and distinct to each socioeconomic group emerged. 6 themes appeared to distinguish between individuals from areas of high and low SED. 4 themes were distinct to participants from areas of high SED: (1) Passivity, (2) Disempowerment, (3) Lack of social support and (4) Short-term focus. 2 themes were distinct to the low SED group: (1) Financial concerns and (2) Location of donor. Conclusions Several of the emerging themes from the high SED individuals relate to an individual's lack of confidence and skill in managing their health and healthcare; themes that are in keeping with low levels of patient activation. Inadequate empowerment of socioeconomically deprived individuals by healthcare practitioners was also described. Financial concerns did not emerge as a barrier from interviews with the high SED group. Interventions aiming to redress the observed socioeconomic inequity should be targeted at both

  11. The sexuality and social performance of androgen-deprived (castrated) men throughout history: implications for modern day cancer patients.

    PubMed

    Aucoin, Michael William; Wassersug, Richard Joel

    2006-12-01

    Androgen-deprivation therapy (ADT) via either surgical or chemical castration is the standard treatment for advanced prostate cancer (PCa). In North America, it is estimated that more than 40,000 men start ADT each year. The side effects of this treatment are extensive and include gynecomastia, erectile dysfunction, and reduced libido. These changes strongly challenge patients' self-identity and sexuality. The historical term for a man who has been castrated is 'eunuch', now a pejorative term implying overall social and sexual impotence. In this paper, we review key historical features of eunuch social performance and sexuality from a variety of cultures in order to assess the validity of contemporary stereotypes of the androgen-deprived male. Data were taken from secondary sources on the history of Byzantium, Roman Antiquity, Early Islamic societies, the Ottoman Empire, Chinese Dynasties, and the Italian Castrati period. This cross-cultural survey shows that castrated men consistently held powerful social positions that yielded great political influence. Many eunuchs were recognized for their loyalty, managerial style, wisdom, and pedagogical skills. Furthermore, rather than being consistently asexual and celibate, they were often sexually active. In certain cultures, they were objects of sexual desire for males, or females, or both. Collectively, the historical accounts suggest that, given the right cultural setting and individual motivation, androgen deprivation may actually enhance rather than hinder both social and sexual performance. We conclude that eunuch history contradicts the presumption that androgen deprivation necessarily leads to social and sexual impotence. The capabilities and accomplishments of eunuchs in the past gives patients on ADT grounds for viewing themselves in a positive light, where they are neither socially impotent nor sexually chaste. PMID:16989928

  12. Genetic and Environmental Processes in Young Children's Resilience and Vulnerability to Socioeconomic Deprivation

    ERIC Educational Resources Information Center

    Kim-Cohen, Julia; Moffitt, Terrie E.; Caspi, Avshalom; Taylor, Alan

    2004-01-01

    Some children exposed to socioeconomic (SES) deprivation are resilient and function better than expected, given the level of deprivation they have experienced. The present study tested genetic and environmental contributions to young children's resilience and vulnerability to SES deprivation. Children's resilience was assessed by the difference…

  13. Current Issues in Maternal and Paternal Deprivation. Unit for Child Studies Selected Papers Number 6.

    ERIC Educational Resources Information Center

    Phillips, Shelley

    An overview of some major current issues in maternal and paternal deprivation is presented. Parts I and II focus on (1) single parents and issues in paternal deprivation and (2) sex stereotyping and issues in maternal deprivation, respectively. More particularly, Part I discusses the effects of divorce and death on children and the problem of…

  14. Double Trouble? The Effects of Sleep Deprivation and Chronotype on Adolescent Affect

    ERIC Educational Resources Information Center

    Dagys, Natasha; McGlinchey, Eleanor L.; Talbot, Lisa S.; Kaplan, Katherine A.; Dahl, Ronald E.; Harvey, Allison G.

    2012-01-01

    Background: Two understudied risk factors that have been linked to emotional difficulties in adolescence are chronotype and sleep deprivation. This study extended past research by using an experimental design to investigate the role of sleep deprivation and chronotype on emotion in adolescents. It was hypothesized that sleep deprivation and an…

  15. Using Indicators of Multiple Deprivation to Demonstrate the Spatial Legacy of Apartheid in South Africa

    ERIC Educational Resources Information Center

    Noble, Michael; Wright, Gemma

    2013-01-01

    This paper presents a spatial analysis of multiple deprivation in South Africa and demonstrates that the most deprived areas in the country are located in the rural former homeland areas. The analysis is undertaken using the datazone level South African Index of Multiple Deprivation which was constructed from the 2001 Census. Datazones are a new…

  16. The Institutionalized Geriatric Patient Considered in a Framework of Developmental Deprivation.

    ERIC Educational Resources Information Center

    Erber, Joan T.

    1979-01-01

    An overview is presented of several areas of deprivation research (animal, child, young adult) and methods of conceptualizing and measuring deprivation is applied to institutionalized geriatric patients. Suggestions are made for more precise approaches to studying and treating deprivation in this population. (Author/SS)

  17. Deprivation in American Affluence: The Theory of Stimulus Addiction.

    ERIC Educational Resources Information Center

    Machell, David F.

    1991-01-01

    Discusses theory of stimulus addiction, a process of human accommodation to stimuli which fosters dependency and may foster addiction. Suggests that a society of affluence may be prone to addictiveness because the more continuous the stimuli the person experiences, the more tolerance is created, and with tolerance comes stimulus deprivation.…

  18. Regional vulnerability of the hippocampus to repeated motor activity deprivation.

    PubMed

    Faraji, Jamshid; Soltanpour, Nabiollah; Moeeini, Reza; Hosseini, Seyed Abedin; Pakdel, Shiva; Moharrerie, Alireza; Arjang, Kaveh; Soltanpour, Nasrin; Metz, Gerlinde A S

    2016-03-15

    Spontaneous vertical and horizontal exploratory movements are integral components of rodent behavior. Little is known, however, about the structural and functional consequences of restricted spontaneous exploration. Here, we report two experiments to probe whether restriction in vertical activity (rearing) in rats could induce neuro-hormonal and behavioral disturbances. Rearing movements in rats were deprived for 3h/day for 30 consecutive days by placing the animal into a circular tunnel task. Rats temporarily deprived of rearing behavior showed elevated plasma corticosterone levels but no detectable psychological distress and/or anxiety-related behavior within an elevated plus maze. However, rats emitted a greater number of 22-kHz ultrasonic vocalizations and spent significantly more time vocalizing than controls when deprived of their rearing behavior. Despite intact spatial performance within wet- and dry-land spatial tasks, rearing-deprived rats also exhibited a significant alteration in search strategies within both spatial tasks along with reduced volume and neuron number in the hippocampal subregion CA2. These data suggest a new approach to test the importance of free exploratory behavior in endocrine and structural manifestations. The results support a central role of the CA2 in spontaneous exploratory behavior and vulnerability to psychological stress. PMID:26723539

  19. Neurodevelopmental Effects of Early Deprivation in Postinstitutionalized Children

    ERIC Educational Resources Information Center

    Pollak, Seth D.; Nelson, Charles A.; Schlaak, Mary F.; Roeber, Barbara J.; Wewerka, Sandi S.; Wiik, Kristen L.; Frenn, Kristin A.; Loman, Michelle M.; Gunnar, Megan R.

    2010-01-01

    The neurodevelopmental sequelae of early deprivation were examined by testing (N = 132) 8- and 9-year-old children who had endured prolonged versus brief institutionalized rearing or rearing in the natal family. Behavioral tasks included measures that permit inferences about underlying neural circuitry. Children raised in institutionalized…

  20. TRAITS OF SCHOOL ACHIEVERS FROM A DEPRIVED BACKGROUND.

    ERIC Educational Resources Information Center

    DAVIDSON, HELEN H.; GREENBERG, JUDITH W.

    A STUDY WAS CONDUCTED TO DETERMINE THE COGNITIVE, AFFECTIVE, MOTIVATIONAL, AND PHYSICAL CHARACTERISTICS OF HIGH-ACHIEVING STUDENTS FROM A DEPRIVED ENVIRONMENT. THE RELATIONSHIP OF THE STUDENT'S SEX TO HIS ACHIEVEMENT STATUS WAS ALSO ASSESSED. THE SUBJECTS, 160 10-YEAR-OLD FIFTH-GRADE NEGRO CHILDREN, WERE DIVIDED INTO LOW-ACHIEVING AND…

  1. Income Satisfaction and Relative Deprivation: An Empirical Link

    ERIC Educational Resources Information Center

    D'Ambrosio, Conchita; Frick, Joachim R.

    2007-01-01

    This paper explores the relationship between two well-established concepts of measuring individual well-being: the concept of "happiness," i.e. self-reported level of satisfaction with income, and "relative deprivation," i.e. the gaps between the individual's income and the incomes of all individuals richer than him. Operationalizing both concepts…

  2. Are You Sleep Deprived? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn JavaScript on. Feature: Sleep Disorders Are You Sleep Deprived? Past Issues / Summer 2015 Table of Contents ... even if you think you've had enough sleep? You might have a sleep disorder. There are ...

  3. Effect of sleep deprivation on the human metabolome.

    PubMed

    Davies, Sarah K; Ang, Joo Ern; Revell, Victoria L; Holmes, Ben; Mann, Anuska; Robertson, Francesca P; Cui, Nanyi; Middleton, Benita; Ackermann, Katrin; Kayser, Manfred; Thumser, Alfred E; Raynaud, Florence I; Skene, Debra J

    2014-07-22

    Sleep restriction and circadian clock disruption are associated with metabolic disorders such as obesity, insulin resistance, and diabetes. The metabolic pathways involved in human sleep, however, have yet to be investigated with the use of a metabolomics approach. Here we have used untargeted and targeted liquid chromatography (LC)/MS metabolomics to examine the effect of acute sleep deprivation on plasma metabolite rhythms. Twelve healthy young male subjects remained in controlled laboratory conditions with respect to environmental light, sleep, meals, and posture during a 24-h wake/sleep cycle, followed by 24 h of wakefulness. Two-hourly plasma samples collected over the 48 h period were analyzed by LC/MS. Principal component analysis revealed a clear time of day variation with a significant cosine fit during the wake/sleep cycle and during 24 h of wakefulness in untargeted and targeted analysis. Of 171 metabolites quantified, daily rhythms were observed in the majority (n = 109), with 78 of these maintaining their rhythmicity during 24 h of wakefulness, most with reduced amplitude (n = 66). During sleep deprivation, 27 metabolites (tryptophan, serotonin, taurine, 8 acylcarnitines, 13 glycerophospholipids, and 3 sphingolipids) exhibited significantly increased levels compared with during sleep. The increased levels of serotonin, tryptophan, and taurine may explain the antidepressive effect of acute sleep deprivation and deserve further study. This report, to our knowledge the first of metabolic profiling during sleep and sleep deprivation and characterization of 24 h rhythms under these conditions, offers a novel view of human sleep/wake regulation. PMID:25002497

  4. Sleep deprivation amplifies striatal activation to monetary reward

    PubMed Central

    Mullin, Benjamin C.; Phillips, Mary L.; Siegle, Greg J.; Buysse, Daniel J.; Forbes, Erika E.; Franzen, Peter L.

    2013-01-01

    Background Sleep loss produces abnormal increases in reward-seeking, though the mechanisms underlying this phenomenon are poorly understood. The present study examined the influence of one night of sleep deprivation on neural responses to a monetary reward task in a sample of late adolescents/young adults. Methods Using a within-subjects crossover design, 27 healthy, right-handed late-adolescents/young adults (16 females, 11 males; mean age 23.1 years) completed functional magnetic resonance imaging following a night of sleep deprivation and following a night of normal sleep. Participants’ recent sleep history was monitored using actigraphy for one week prior to each sleep condition. Results Following sleep deprivation, participants exhibited increased activity in the ventral striatum and reduced deactivation in medial prefrontal cortex during the winning of monetary reward, relative to the same task following normal sleep conditions. Shorter total sleep time over the five nights before the sleep deprived testing condition was associated with reduced deactivation in the medial prefrontal cortex during reward. Conclusions These findings support the hypothesis that sleep loss produces aberrant functioning in reward neural circuitry, increasing the salience of positively-reinforcing stimuli. Aberrant reward functioning related to insufficient sleep may contribute to the development and maintenance of reward dysfunction-related disorders, such as compulsive gambling, eating, substance abuse, and mood disorders. PMID:23286303

  5. Behavior Problems in Children Adopted from Psychosocially Depriving Institutions

    ERIC Educational Resources Information Center

    Merz, Emily C.; McCall, Robert B.

    2010-01-01

    Behavior problems were investigated in 342 6- to 18-year-old children adopted from psychosocially depriving Russian institutions that provided adequate physical resources but not consistent, responsive caregiving. Results indicated that attention and externalizing problems were the most prevalent types of behavior problems in the sample as a…

  6. Deprivation, Social Exclusion and Subjective Well-Being

    ERIC Educational Resources Information Center

    Bellani, Luna; D'Ambrosio, Conchita

    2011-01-01

    This paper aims at investigating empirically the relationship between self-declared satisfaction with life and an individual's well-being as measured by the indices of deprivation and social exclusion proposed in the income distribution literature. Results on European countries show that life satisfaction decreases with an increase in deprivation…

  7. Auditory, Tactile, and Audiotactile Information Processing Following Visual Deprivation

    ERIC Educational Resources Information Center

    Occelli, Valeria; Spence, Charles; Zampini, Massimiliano

    2013-01-01

    We highlight the results of those studies that have investigated the plastic reorganization processes that occur within the human brain as a consequence of visual deprivation, as well as how these processes give rise to behaviorally observable changes in the perceptual processing of auditory and tactile information. We review the evidence showing…

  8. [Support for teenage pregnancies and early emotional deprivation].

    PubMed

    Andro, Gwénäelle

    2016-01-01

    The perinatal psychology and psychiatry unit of Caen university hospital has put in place two systematic intervention protocols relating to pregnancy: teenage pregnancy and denial of pregnancy. Professionals are particularly concerned with teenagers with a history of early emotional deprivation and mistreatment, with the spectre of repetition. A partnership with a motherhood centre helps all concerned to work together to build resilience. PMID:27444534

  9. Citicoline retards myopia progression following form deprivation in guinea pigs.

    PubMed

    Mao, Junfeng; Liu, Shuangzhen; Fu, Chunyan

    2016-06-01

    The retinal dopaminergic system is involved in the myopic shift following form deprivation. Citicoline has been demonstrated to stimulate the dopaminergic system in the brain and retina. Furthermore, citicoline has been used in many neurogenic diseases, such as senile cognitive impairment, stroke and Parkinson's disease as well as in amblyopia and glaucoma. Our aim was to investigate the effect of citicoline on the refractive state and retinal dopamine level in form deprivation myopia of guinea pigs. Guinea pigs, at an age of four weeks, were randomly divided into normal control, deprivation, deprived + citicoline and deprived + vehicle groups. Form deprivation myopia was induced by a translucent eye shield covering the right eye. Citicoline was injected intraperitoneally twice a day (500 mg/kg, 9 am and 9 pm) for 10 days. In vitro, retinal explants were cultured with citicoline for 24 h, with a final citicoline concentration of 100 µmol/L. The ocular refractive parameters and retinal dopamine content were measured. After occlusion for 10 days, the form-deprived eyes became myopic with an increase in axial length and a decrease in retinal dopamine content. The intraperitoneal injection of citicoline reduced the myopic degree (from -3.25 ± 0.77D to -0.62 ± 0.47D, P < 0.001) and partially raised retinal dopamine levels (from 0.55 ± 0.21 ng to 0.81 ± 0.24 ng, P < 0.01) in the form-deprived eyes. After 24 h of culturing retinal explants with citicoline, retinal dopamine content increased significantly (from 0.42 ± 0.14 ng to 0.62 ± 0.21 ng, P < 0.05). These results demonstrated that an intraperitoneal injection of citicoline could retard the myopic shift induced by form deprivation in guinea pigs, which was mediated by an increase in the retinal dopamine levels. PMID:26979720

  10. [Experimentation with a socioeconomic deprivation index in Basilicata].

    PubMed

    Valerio, M; Vitullo, F

    2000-01-01

    Deprivation measures have become important tools, in microarea and small area studies, both for examining variations in health and health care, and for planning services and allocating resources. To value the level of municipal deprivation in Basilicata (Southern Italy), 1991 Census data were used. As a first analytic step, variables selected as deprivation measures were calculated. "Elderly" variable was included at the first step since it was considered as an indicator of social burden and need. As a second analytic step, factorial analysis was performed in order to help in selecting the most valuable ones. The final choice led to five variables (elderly, low education, unemployment, no indoor bathroom, lone parent with children) which were combined in an Index of Deprived Area (IAS). The IAS showed a variation between -5.4 and 7.4. To validate the IAS, the municipal level of income was used: the index increased with decreasing income (r = -0.5). Municipalities were then ranked according to their IAS (decreasing) and divided into five deprivation categories, with about equal population number in each group. After excluding the "elderly" indicator, the ranking order showed irrelevant changes (modified IAS). Overall, the IAS seemed to well describe the difference among Municipalities, particularly between the first quintile (54 small towns with high prevalence of old people) and the last group (the urban area of the region). The developed tool and the obtained results may be used by administrators and health/social workers and professionals in charge of the Regional Epidemiological Observatory to improve the selection of health and social indicators for Local Health Authorities and Municipalities. PMID:11189477

  11. Changes in Plasma Lipids during Exposure to Total Sleep Deprivation

    PubMed Central

    Chua, Eric Chern-Pin; Shui, Guanghou; Cazenave-Gassiot, Amaury; Wenk, Markus R.; Gooley, Joshua J.

    2015-01-01

    Study Objectives: The effects of sleep loss on plasma lipids, which play an important role in energy homeostasis and signaling, have not been systematically examined. Our aim was to identify lipid species in plasma that increase or decrease reliably during exposure to total sleep deprivation. Design: Twenty individuals underwent sleep deprivation in a laboratory setting. Blood was drawn every 4 h and mass spectrometry techniques were used to analyze concentrations of 263 lipid species in plasma, including glycerolipids, glycerophospholipids, sphingolipids, and sterols. Setting: Chronobiology and Sleep Laboratory, Duke-NUS Graduate Medical School. Participants: Healthy ethnic-Chinese males aged 21–28 y (n = 20). Interventions: Subjects were kept awake for 40 consecutive hours. Measurements and Results: Each metabolite time series was modeled as a sum of sinusoidal (circadian) and linear components, and we assessed whether the slope of the linear component differed from zero. More than a third of all individually analyzed lipid profiles exhibited a circadian rhythm and/or a linear change in concentration during sleep deprivation. Twenty-five lipid species showed a linear and predominantly unidirectional trend in concentration levels that was consistent across participants. Choline plasmalogen levels decreased, whereas several phosphatidylcholine (PC) species and triacylglycerides (TAG) carrying polyunsaturated fatty acids increased. Conclusions: The decrease in choline plasmalogen levels during sleep deprivation is consistent with prior work demonstrating that these lipids are susceptible to degradation by oxidative stress. The increase in phosphatidylcholines and triacylglycerides suggests that sleep loss might modulate lipid metabolism, which has potential implications for metabolic health in individuals who do not achieve adequate sleep. Citation: Chua EC, Shui G, Cazenave-Gassiot A, Wenk MR, Gooley JJ. Changes in plasma lipids during exposure to total sleep

  12. Sex-dependent effects of sleep deprivation on myocardial sensitivity to ischemic injury.

    PubMed

    Zoladz, Phillip R; Krivenko, Anna; Eisenmann, Eric D; Bui, Albert D; Seeley, Sarah L; Fry, Megan E; Johnson, Brandon L; Rorabaugh, Boyd R

    2016-01-01

    Sleep deprivation is associated with increased risk of myocardial infarction. However, it is unknown whether the effects of sleep deprivation are limited to increasing the likelihood of experiencing a myocardial infarction or if sleep deprivation also increases the extent of myocardial injury. In this study, rats were deprived of paradoxical sleep for 96 h using the platform-over-water method. Control rats were subjected to the same condition except the control platform was large enough for the rats to sleep. Hearts from sleep deprived and control rats were subjected to 20 min ischemia on a Langendorff isolated heart system. Infarct size and post ischemic recovery of contractile function were unaffected by sleep deprivation in male hearts. In contrast, hearts from sleep-deprived females exhibited significantly larger infarcts than hearts from control females. Post ischemic recovery of rate pressure product and + dP/dT were significantly attenuated by sleep deprivation in female hearts, and post ischemic recovery of end diastolic pressure was significantly elevated in hearts from sleep deprived females compared to control females, indicating that post ischemic recovery of both systolic and diastolic function were worsened by sleep deprivation. These data provide evidence that sleep deprivation increases the extent of ischemia-induced injury in a sex-dependent manner. PMID:26953626

  13. Decreased attentional responsivity during sleep deprivation: orienting response latency, amplitude, and habituation.

    PubMed

    McCarthy, M E; Waters, W F

    1997-02-01

    Ever increasing societal demands for uninterrupted work are causing unparalleled amounts of sleep deprivation among workers. Sleep deprivation has been linked to safety problems ranging from medical misdiagnosis to industrial and vehicular accidents. Microsleeps (very brief intrusions of sleep into wakefulness) are usually cited as the cause of the performance decrements during sleep deprivation. Changes in a more basic physiological phenomenon, attentional shift, were hypothesized to be additional factors in performance declines. The current study examined the effects of 36 hours of sleep deprivation on the electrodermal-orienting response (OR), a measure of attentional shift or capture. Subjects were 71 male undergraduate students, who were divided into sleep deprivation and control (non-sleep deprivation) groups. The expected negative effects of sleep deprivation on performance were noted in increased reaction times and increased variability in the sleep-deprived group on attention-demanding cognitive tasks. OR latency was found to be significantly delayed after sleep deprivation, OR amplitude was significantly decreased, and habituation of the OR was significantly faster during sleep deprivation. These findings indicate impaired attention, the first revealing slowed shift of attention to novel stimuli, the second indicating decreased attentional allocation to stimuli, and the third revealing more rapid loss of attention to repeated stimuli. These phenomena may be factors in the impaired cognitive performance seen during sleep deprivation. PMID:9143071

  14. Latent deprivation among people who are employed, unemployed, or out of the labor force.

    PubMed

    Paul, Karsten I; Geithner, Eva; Moser, Klaus

    2009-10-01

    Using a Web-based survey, the authors tested M. Jahoda's (1981, 1982, 1997) latent deprivation model among employed, unemployed, and out-of-the-labor-force (OLF) people. The model predicted that employment is the main provider of 5 specific subconstructs of experience important to mental health: time structure, social contact, collective purpose, status, and activity. As expected, deprivation of these latent functions correlated with distress not only among employed and unemployed people, but also among OLF people. OLF people reported significantly more latent deprivation than did employed people, but they reported significantly less latent deprivation than did unemployed people. Furthermore, latent deprivation mediated the negative effects of unemployment and OLF status on mental health. When the authors statistically controlled the influence of manifest deprivation, the effect of latent deprivation on mental health remained stable. PMID:19943399

  15. Which is the best deprivation predictor of foetal and infant mortality rates?

    PubMed

    Joyce, R; Webb, R; Peacock, J L; Stirland, H

    2000-01-01

    This study investigates which, if any, population-based indicator of deprivation best predicts foetal and infant mortality rates in England. For the year 1995, the deprivation levels of 364 English Local Authorities were compared; using the three commonly used indicators, Jarman score, Townsend score and percentage unemployed. The predictive value of these for stillbirth, neonatal and infant mortality rates was then calculated. The three deprivation indicators were highly inter-correlated (r=0.866-0.924). For each mortality rate, the correlation with deprivation did not differ significantly for the three indicators of deprivation. We conclude, when comparing these outcomes in different areas of England, that any of the three deprivation indicators may be used to adjust for deprivation. PMID:10787021

  16. Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling.

    PubMed

    Hines, D J; Schmitt, L I; Hines, R M; Moss, S J; Haydon, P G

    2013-01-01

    Major depressive disorder is a debilitating condition with a lifetime risk of ten percent. Most treatments take several weeks to achieve clinical efficacy, limiting the ability to bring instant relief needed in psychiatric emergencies. One intervention that rapidly alleviates depressive symptoms is sleep deprivation; however, its mechanism of action is unknown. Astrocytes regulate responses to sleep deprivation, raising the possibility that glial signaling mediates antidepressive-like actions of sleep deprivation. Here, we found that astrocytic signaling to adenosine (A1) receptors was required for the robust reduction of depressive-like behaviors following 12 hours of sleep deprivation. As sleep deprivation activates synaptic A1 receptors, we mimicked the effect of sleep deprivation on depression phenotypes by administration of the A1 agonist CCPA. These results provide the first mechanistic insight into how sleep deprivation impacts mood, and provide a novel pathway for rapid antidepressant development by modulation of glial signaling in the brain. PMID:23321809

  17. Neighborhood Deprivation Is Strongly Associated with Participation in a Population-Based Health Check

    PubMed Central

    Bender, Anne Mette; Kawachi, Ichiro; Jørgensen, Torben; Pisinger, Charlotta

    2015-01-01

    Background We sought to examine whether neighborhood deprivation is associated with participation in a large population-based health check. Such analyses will help answer the question whether health checks, which are designed to meet the needs of residents in deprived neighborhoods, may increase participation and prove to be more effective in preventing disease. In Europe, no study has previously looked at the association between neighborhood deprivation and participation in a population-based health check. Methods The study population comprised 12,768 persons invited for a health check including screening for ischemic heart disease and lifestyle counseling. The study population was randomly drawn from a population of 179,097 persons living in 73 neighborhoods in Denmark. Data on neighborhood deprivation (percentage with basic education, with low income and not in work) and individual socioeconomic position were retrieved from national administrative registers. Multilevel regression analyses with log links and binary distributions were conducted to obtain relative risks, intraclass correlation coefficients and proportional change in variance. Results Large differences between neighborhoods existed in both deprivation levels and neighborhood health check participation rate (mean 53%; range 35-84%). In multilevel analyses adjusted for age and sex, higher levels of all three indicators of neighborhood deprivation and a deprivation score were associated with lower participation in a dose-response fashion. Persons living in the most deprived neighborhoods had up to 37% decreased probability of participating compared to those living in the least deprived neighborhoods. Inclusion of individual socioeconomic position in the model attenuated the neighborhood deprivation coefficients, but all except for income deprivation remained statistically significant. Conclusion Neighborhood deprivation was associated with participation in a population-based health check in a dose

  18. Sleep Duration and Area-Level Deprivation in Twins

    PubMed Central

    Watson, Nathaniel F.; Horn, Erin; Duncan, Glen E.; Buchwald, Dedra; Vitiello, Michael V.; Turkheimer, Eric

    2016-01-01

    Study Objectives: We used quantitative genetic models to assess whether area-level deprivation as indicated by the Singh Index predicts shorter sleep duration and modifies its underlying genetic and environmental contributions. Methods: Participants were 4,218 adult twin pairs (2,377 monozygotic and 1,841 dizygotic) from the University of Washington Twin Registry. Participants self-reported habitual sleep duration. The Singh Index was determined by linking geocoding addresses to 17 indicators at the census-tract level using data from Census of Washington State and Census Tract Cartographic Boundary Files from 2000 and 2010. Data were analyzed using univariate and bivariate genetic decomposition and quantitative genetic interaction models that assessed A (additive genetics), C (common environment), and E (unique environment) main effects of the Singh Index on sleep duration and allowed the magnitude of residual ACE variance components in sleep duration to vary with the Index. Results: The sample had a mean age of 38.2 y (standard deviation [SD] = 18), and was predominantly female (62%) and Caucasian (91%). Mean sleep duration was 7.38 h (SD = 1.20) and the mean Singh Index score was 0.00 (SD = 0.89). The heritability of sleep duration was 39% and the Singh Index was 12%. The uncontrolled phenotypic regression of sleep duration on the Singh Index showed a significant negative relationship between area-level deprivation and sleep length (b = −0.080, P < 0.001). Every 1 SD in Singh Index was associated with a ∼4.5 min change in sleep duration. For the quasi-causal bivariate model, there was a significant main effect of E (b0E = −0.063; standard error [SE] = 0.30; P < 0.05). Residual variance components unique to sleep duration were significant for both A (b0Au = 0.734; SE = 0.020; P < 0.001) and E (b0Eu = 0.934; SE = 0.013; P < 0.001). Conclusions: Area-level deprivation has a quasi-causal association with sleep duration, with greater deprivation being related to

  19. Health-Risk Behaviour in Deprived Neighbourhoods Compared with Non-Deprived Neighbourhoods: A Systematic Literature Review of Quantitative Observational Studies

    PubMed Central

    Algren, Maria Holst; Bak, Carsten Kronborg; Berg-Beckhoff, Gabriele; Andersen, Pernille Tanggaard

    2015-01-01

    Background There has been increasing interest in neighbourhoods’ influence on individuals’ health-risk behaviours, such as smoking, alcohol consumption, physical activity and diet. The aim of this review was to systematically review recent studies on health-risk behaviour among adults who live in deprived neighbourhoods compared with those who live in non-deprived neighbourhoods and to summarise what kind of operationalisations of neighbourhood deprivation that were used in the studies. Methods PRISMA guidelines for systematic reviews were followed. Systematic searches were performed in PubMed, Embase, Web of Science and Sociological Abstracts using relevant search terms, Boolean operators, and truncation, and reference lists were scanned. Quantitative observational studies that examined health-risk behaviour in deprived neighbourhoods compared with non-deprived neighbourhoods were eligible for inclusion. Results The inclusion criteria were met by 22 studies. The available literature showed a positive association between smoking and physical inactivity and living in deprived neighbourhoods compared with non-deprived neighbourhoods. In regard to low fruit and vegetable consumption and alcohol consumption, the results were ambiguous, and no clear differences were found. Numerous different operationalisations of neighbourhood deprivation were used in the studies. Conclusion Substantial evidence indicates that future health interventions in deprived neighbourhoods should focus on smoking and physical inactivity. We suggest that alcohol interventions should be population based rather than based on the specific needs of deprived neighbourhoods. More research is needed on fruit and vegetable consumption. In future studies, the lack of a uniform operationalisation of neighbourhood deprivation must be addressed. PMID:26506251

  20. Sleep deprivation during a specific 3-hour time window post-training impairs hippocampal synaptic plasticity and memory

    PubMed Central

    Prince, Toni-Moi; Wimmer, Mathieu; Choi, Jennifer; Havekes, Robbert; Aton, Sara; Abel, Ted

    2014-01-01

    Sleep deprivation disrupts hippocampal function and plasticity. In particular, long-term memory consolidation is impaired by sleep deprivation, suggesting that a specific critical period exists following learning during which sleep is necessary. To elucidate the impact of sleep deprivation on long-term memory consolidation and synaptic plasticity, long-term memory was assessed when mice were sleep deprived following training in the hippocampus-dependent object place recognition task. We found that 3 hours of sleep deprivation significantly impaired memory when deprivation began 1 hour after training. In contrast, 3 hours of deprivation beginning immediately post-training did not impair spatial memory. Furthermore, a 3-hour sleep deprivation beginning 1 hour after training impaired hippocampal long-term potentiation (LTP), whereas sleep deprivation immediately after training did not affect LTP. Together, our findings define a specific 3-hour critical period, extending from 1 to 4 hours after training, during which sleep deprivation impairs hippocampal function. PMID:24380868

  1. Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Background Prostate cancer is the most common cancer in older men in the United States (USA) and Western Europe. Androgen deprivation (AD) constitutes, in most cases, the first-line of treatment for these cases. The negative impact of CAD in quality of life, secondary to the adverse events of sustained hormone deprivation, plus the costs of this therapy, motivated the intermittent treatment approach. The objective of this study is to to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy and adverse events profile of intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. Methods Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), cancer-specific survival (CSS), time to progression (TTP) and adverse events. We performed a meta-analysis (MA) of the published data. The results were expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% Confidence Intervals (CI 95%). Results The final analysis included 13 trials comprising 6,419 patients with hormone-sensitive prostate cancer. TTP was similar in patients who received intermittent androgen deprivation (IAD) or continuous androgen deprivation (CAD) (fixed effect: HR = 1.04; CI 95% = 0.96 to 1.14; p = 0.3). OS and CSS were also similar in patients treated with IAD or CAD (OS: fixed effect: HR = 1.02; CI 95% = 0.95 to 1.09; p = 0.56 and CSS: fixed effect: HR = 1.06; CI 95% = 0.96 to 1.18; p = 0.26). Conclusion Overall survival was similar between IAD and CAD in patients with locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. Data on CSS are weak and the benefits of IAD on this outcome remain uncertain. Impact in QoL was similar for both groups, however, sexual activity scores were higher and the incidence of hot flushes was lower in

  2. Effects of Extreme Sleep Deprivation on Human Performance

    SciTech Connect

    Tuan Tran; Kimberly R. Raddatz; Elizabeth T. Cady; Bradford Amstutz; Pete D. Elgin; Christopher Vowels; Gerald Deehan

    2007-04-01

    Sleep is a fundamental recuperative process for the nervous system. Disruption of this homeostatic drive can lead to severe impairments of the operator’s ability to perceive, recognize, and respond to emergencies and/or unanticipated events, putting the operator at risk. Therefore, establishing a comprehensive understanding of how sleep deprivation influences human performance is essential in order to counter fatigue or to develop mitigation strategies. The goal of the present study was to examine the psychological effects of prolonged sleep deprivation (approx. 75 hrs) over a four-day span on a general aviation pilot flying a fixed-based flight simulator. During the study, a series of tasks were employed every four hours in order to examine the pilot’s perceptual and higher level cognitive abilities. Overall, results suggest that the majority of cognitive and perceptual degradation occurs between 30-40 hours into the flight. Limitations and future research directions are also discussed.

  3. Auditory deprivation modifies biological rhythms in the golden hamster.

    PubMed

    Cutrera, R; Pedemonte, M; Vanini, G; Goldstein, N; Savorini, D; Cardinali, D P; Velluti, R A

    2000-11-01

    To assess to what extent auditory sensory deprivation affects biological rhythmicity, sleep/wakefulness cycle and 24 h rhythm in locomotor activity were examined in golden hamsters after bilateral cochlear lesion. An increase in total sleep time as well as a decrease in wakefulness (W) were associated to an augmented number of W episodes, as well as of slow wave sleep (SWS) and paradoxical sleep (PS) episodes in deaf hamsters. The number of episodes of the three behavioural states and the percent duration of W and SWS increased significantly during the light phase of daily photoperiod only. Lower amplitudes of locomotor activity rhythm and a different phase angle as far as light off were found in deaf hamsters kept either under light-dark photoperiod or in constant darkness. Period of locomotor activity remained unchanged after cochlear lesions. The results indicate that auditory deprivation disturbs photic synchronization of rhythms with little effect on the clock timing mechanism itself. PMID:11116570

  4. Octopamine connects nutrient cues to lipid metabolism upon nutrient deprivation

    PubMed Central

    Tao, Jun; Ma, Yi-Cheng; Yang, Zhong-Shan; Zou, Cheng-Gang; Zhang, Ke-Qin

    2016-01-01

    Starvation is probably the most common stressful situation in nature. In vertebrates, elevation of the biogenic amine norepinephrine levels is common during starvation. However, the precise role of norepinephrine in nutrient deprivation remains largely unknown. We report that in the free-living nematode Caenorhabditis elegans, up-regulation of the biosynthesis of octopamine, the invertebrate counterpart of norepinephrine, serves as a mechanism to adapt to starvation. During nutrient deprivation, the nuclear receptor DAF-12, known to sense nutritional cues, up-regulates the expression of tbh-1 that encodes tyramine β-hydroxylase, a key enzyme for octopamine biosynthesis, in the RIC neurons. Octopamine induces the expression of the lipase gene lips-6 via its receptor SER-3 in the intestine. LIPS-6, in turn, elicits lipid mobilization. Our findings reveal that octopamine acts as an endocrine regulator linking nutrient cues to lipolysis to maintain energy homeostasis, and suggest that such a mechanism may be evolutionally conserved in diverse organisms. PMID:27386520

  5. Alcohol use, socioeconomic deprivation and ethnicity in older people

    PubMed Central

    Rao, Rahul; Schofield, Peter; Ashworth, Mark

    2015-01-01

    Objectives This study explores the relationship between alcohol consumption, health, ethnicity and socioeconomic deprivation. Participants 27 991 people aged 65 and over from an inner-city population, using a primary care database. Primary and Secondary Outcome Measures Primary outcome measures were alcohol use and misuse (>21 units per week for men and >14 for units per week women). Results Older people of black and minority ethnic (BME) origin from four distinct ethnic groups comprised 29% of the sample. A total of 9248 older drinkers were identified, of whom 1980 (21.4%) drank above safe limits. Compared with older drinkers, older unsafe drinkers contained a higher proportion of males, white and Irish ethnic groups and a lower proportion of Caribbean, African and Asian groups. For older drinkers, the strongest independent predictors of higher alcohol consumption were younger age, male gender and Irish ethnicity. Independent predictors of lower alcohol consumption were Asian, black Caribbean and black African ethnicity. Socioeconomic deprivation and comorbidity were not significant predictors of alcohol consumption in older drinkers. For older unsafe drinkers, the strongest predictor variables were younger age, male gender and Irish ethnicity; comorbidity was not a significant predictor. Lower socioeconomic deprivation was a significant predictor of unsafe consumption whereas African, Caribbean and Asian ethnicity were not. Conclusions Although under-reporting in high-alcohol consumption groups and poor health in older people who have stopped or controlled their drinking may have limited the interpretation of our results, we suggest that closer attention is paid to ‘young older’ male drinkers, as well as to older drinkers born outside the UK and those with lower levels of socioeconomic deprivation who are drinking above safe limits. PMID:26303334

  6. Sleep deprivation in junior doctors--house officers in Singapore.

    PubMed

    Puvanendran, K; Venkatramani, Jayant; Jain, Amit; Farid, Mohamad

    2005-01-01

    House officers are known to endure marked levels of sleep deprivation in administration of their duties. We aim to establish sleep patterns of local house officers while on the job and the impact it might have on their mood and sleepiness state. We also studied their sleep during their final year of medical school and pre-university for identification of any prior sleep deprivation. Questionnaires were used to assess sleep and mood change. Sleepiness levels on the day after call were assessed using the Stamford Sleepiness Scale. Subjects were found to sleep a median of only 1.0 (+/- 2.0) h per night on call and 6.0 h (+/- 1.0) per non-call night. They suffered median of 5 interruptions (+/- 5) during sleep on one night call. Night call was found to adversely affect mood in 89.5% of the subjects while daytime sleepiness levels following call were found to increase the more the time spent at work after call. Subjects were found to have had 6.5 h (+/- 1.0) of sleep per night during final year of medical school and 8.0 h (+/- 1.0) in final year of pre-university. House officers enter the profession chronically sleep-deprived. The call schedule and general work regime further add to the existent sleep deprivation and may have adverse consequences on patient care and doctor's health. This calls for measures to be instituted for provision of proper sleep and work hours for them. PMID:15732315

  7. Effect of 24 Hours of Sleep Deprivation on Auditory and Linguistic Perception: A Comparison among Young Controls, Sleep-Deprived Participants, Dyslexic Readers, and Aging Adults

    ERIC Educational Resources Information Center

    Fostick, Leah; Babkoff, Harvey; Zukerman, Gil

    2014-01-01

    Purpose: To test the effects of 24 hr of sleep deprivation on auditory and linguistic perception and to assess the magnitude of this effect by comparing such performance with that of aging adults on speech perception and with that of dyslexic readers on phonological awareness. Method: Fifty-five sleep-deprived young adults were compared with 29…

  8. Deprivation of Liberty: Collected Guidance Various authors Deprivation of Liberty: Collected Guidance 400pp £29.95 Law Society Publishing 9781784460433 1784460435 [Formula: see text].

    PubMed

    2016-04-20

    Deprivation of liberty can be a confusing subject for lawyers and healthcare professionals alike. Part of the difficulty in understanding and applying deprivation of liberty safeguards is that there is a complex set of regulations and it can be challenging to find specific information from the various sources of published guidance. PMID:27097198

  9. Relative deprivation and psychopathology of Chinese college students.

    PubMed

    Zhang, Jie; Tao, Mengke

    2013-09-25

    Previous researchers have studied the relationship between mental disorder and major demographic variables, but the study on the relationship between relative poverty or relative deprivation, a subjectively perceived status in comparison with people around, and psychopathology is rare. Data for this study were obtained from a survey research conducted on a university campus in Beijing China, between 2007 and 2011, with a total of 5925 college students who participated in the surveys over the past five years. According to the Strain Theory of suicide we hypothesized that the stronger the relative deprivation, the higher the level of depression for the students and the higher the degree of suicidal ideation the students would experience. Findings indicated that relative deprivation is significantly correlated with suicidal ideation, positively related with depression and negatively related to social support. It is proposed that reduction of psychological strains might be an effective procedure to reduce college students' psychopathology and increase their positive psychological feelings such as self-perceived social support. PMID:23714373

  10. Social Deprivation and the HPA Axis in Early Development

    PubMed Central

    Koss, Kalsea J.; Hostinar, Camelia E.; Donzella, Bonny; Gunnar, Megan R.

    2014-01-01

    Growing evidence suggests that early social deprivation impacts the activity of the hypothalamic-pituitary-adrenocortical axis. Early adverse care in the form of institutional or orphanage care provides a human model for early social deprivation. The present study examined changes in diurnal cortisol during the transition to family care in the first two years post-adoption. Children adopted between 15 and 36 months from institutional care were examined four times during their first two years post-adoption (N=58). Comparison groups included same-aged peers reared in their birth families (N=50) and children adopted during their first year from overseas foster care (N=47). Children provided daily cortisol samples at roughly 2, 9, 17, and 25 months post-adoption. Post-institutionalized and post-foster care children exhibited less steep diurnal cortisol compared to non-adopted same-aged peers; these differences did not diminish across the two year period. For post-institutionalized children, lower social care quality in institutions was associated with less steep cortisol slopes. Lastly, shallower diurnal cortisol was a mediator between adoption status and increased behavioral problems two years post-adoption. Consistent with the non-human primate literature, early social deprivation may contribute to early programming of the HPA axis. PMID:25150507

  11. Genotype-dependent lifespan effects in peptone deprived Caenorhabditis elegans

    PubMed Central

    Stastna, Jana J.; Snoek, L. Basten; Kammenga, Jan E.; Harvey, Simon C.

    2015-01-01

    Dietary restriction appears to act as a general non-genetic mechanism that can robustly prolong lifespan. There have however been reports in many systems of cases where restricted food intake either shortens, or does not affect, lifespan. Here we analyze lifespan and the effect of food restriction via deprived peptone levels on lifespan in wild isolates and introgression lines (ILs) of the nematode Caenorhabditis elegans. These analyses identify genetic variation in lifespan, in the effect of this variation in diet on lifespan and also in the likelihood of maternal, matricidal, hatching. Importantly, in the wild isolates and the ILs, we identify genotypes in which peptone deprivation mediated dietary restriction reduces lifespan. We also identify, in recombinant inbred lines, a locus that affects maternal hatching, a phenotype closely linked to dietary restriction in C. elegans. These results indicate that peptone deprivation mediated dietary restriction affects lifespan in C. elegans in a genotype-dependent manner, reducing lifespan in some genotypes. This may operate by a mechanism similar to dietary restriction. PMID:26539794

  12. Functional imaging correlates of impaired distractor suppression following sleep deprivation.

    PubMed

    Kong, Danyang; Soon, Chun Siong; Chee, Michael W L

    2012-05-15

    Sleep deprivation (SD) has been shown to affect selective attention but it is not known how two of its component processes: target enhancement and distractor suppression, are affected. To investigate, young volunteers either attended to houses or were obliged to ignore them (when attending to faces) while viewing superimposed face-house pictures. MR signal enhancement and suppression in the parahippocampal place area (PPA) were determined relative to a passive viewing control condition. Sleep deprivation was associated with lower PPA activation across conditions. Critically SD specifically impaired distractor suppression in selective attention, leaving target enhancement relatively preserved. These findings parallel some observations in cognitive aging. Additionally, following SD, attended houses were not significantly better recognized than ignored houses in a post-experiment test of recognition memory contrasting with the finding of superior recognition of attended houses in the well-rested state. These results provide evidence for co-encoding of distracting information with targets into memory when one is sleep deprived. PMID:22426349

  13. Sleep deprivation impairs inhibitory control during wakefulness in adult sleepwalkers.

    PubMed

    Labelle, Marc-Antoine; Dang-Vu, Thien Thanh; Petit, Dominique; Desautels, Alex; Montplaisir, Jacques; Zadra, Antonio

    2015-12-01

    Sleepwalkers often complain of excessive daytime somnolence. Although excessive daytime somnolence has been associated with cognitive impairment in several sleep disorders, very few data exist concerning sleepwalking. This study aimed to investigate daytime cognitive functioning in adults diagnosed with idiopathic sleepwalking. Fifteen sleepwalkers and 15 matched controls were administered the Continuous Performance Test and Stroop Colour-Word Test in the morning after an overnight polysomnographic assessment. Participants were tested a week later on the same neuropsychological battery, but after 25 h of sleep deprivation, a procedure known to precipitate sleepwalking episodes during subsequent recovery sleep. There were no significant differences between sleepwalkers and controls on any of the cognitive tests administered under normal waking conditions. Testing following sleep deprivation revealed significant impairment in sleepwalkers' executive functions related to inhibitory control, as they made more errors than controls on the Stroop Colour-Word Test and more commission errors on the Continuous Performance Test. Sleepwalkers' scores on measures of executive functions were not associated with self-reported sleepiness or indices of sleep fragmentation from baseline polysomnographic recordings. The results support the idea that sleepwalking involves daytime consequences and suggest that these may also include cognitive impairments in the form of disrupted inhibitory control following sleep deprivation. These disruptions may represent a daytime expression of sleepwalking's pathophysiological mechanisms. PMID:26087833

  14. Lipidomic Analysis of Chlamydomonas reinhardtii under Nitrogen and Sulfur Deprivation

    PubMed Central

    Yang, Dawei; Song, Donghui; Kind, Tobias; Ma, Yan; Hoefkens, Jens; Fiehn, Oliver

    2015-01-01

    Chlamydomonas reinhardtii accumulates lipids under complete nutrient starvation conditions while overall growth in biomass stops. In order to better understand biochemical changes under nutrient deprivation that maintain production of algal biomass, we used a lipidomic assay for analyzing the temporal regulation of the composition of complex lipids in C. reinhardtii in response to nitrogen and sulfur deprivation. Using a chip-based nanoelectrospray direct infusion into an ion trap mass spectrometer, we measured a diversity of lipid species reported for C. reinhardtii, including PG phosphatidylglycerols, PI Phosphatidylinositols, MGDG monogalactosyldiacylglycerols, DGDG digalactosyldiacylglycerols, SQDG sulfoquinovosyldiacylglycerols, DGTS homoserine ether lipids and TAG triacylglycerols. Individual lipid species were annotated by matching mass precursors and MS/MS fragmentations to the in-house LipidBlast mass spectral database and MS2Analyzer. Multivariate statistics showed a clear impact on overall lipidomic phenotypes on both the temporal and the nutrition stress level. Homoserine-lipids were found up-regulated at late growth time points and higher cell density, while triacyclglycerols showed opposite regulation of unsaturated and saturated fatty acyl chains under nutritional deprivation. PMID:26375463

  15. Sleep Deprivation Attack Detection in Wireless Sensor Network

    NASA Astrophysics Data System (ADS)

    Bhattasali, Tapalina; Chaki, Rituparna; Sanyal, Sugata

    2012-02-01

    Deployment of sensor network in hostile environment makes it mainly vulnerable to battery drainage attacks because it is impossible to recharge or replace the battery power of sensor nodes. Among different types of security threats, low power sensor nodes are immensely affected by the attacks which cause random drainage of the energy level of sensors, leading to death of the nodes. The most dangerous type of attack in this category is sleep deprivation, where target of the intruder is to maximize the power consumption of sensor nodes, so that their lifetime is minimized. Most of the existing works on sleep deprivation attack detection involve a lot of overhead, leading to poor throughput. The need of the day is to design a model for detecting intrusions accurately in an energy efficient manner. This paper proposes a hierarchical framework based on distributed collaborative mechanism for detecting sleep deprivation torture in wireless sensor network efficiently. Proposed model uses anomaly detection technique in two steps to reduce the probability of false intrusion.

  16. Metabolic, Endocrine, and Immune Consequences of Sleep Deprivation

    PubMed Central

    AlDabal, Laila; BaHammam, Ahmed S

    2011-01-01

    Over the last three to four decades, it has been observed that the average total hours of sleep have decreased to less than seven hours per person per night. Concomitantly, global figures relating to obesity and diabetes mellitus have increased in an alarming fashion in adults and children, and it has been hypothesized that neuro-hormonal changes accompanying this behavioral sleep deprivation may lead to insulin resistance and, subsequently, to diabetes mellitus. Sleep deprivation has been associated with multiple physiological changes, including increased cortisol and ghrelin levels, decreased leptin levels and impaired glucose metabolism. Experimental studies have also shown an increase in inflammatory and pro-inflammatory markers, which are indicators of body stress, under sleep deprivation. This review elaborates further on this hypothesis, exploring the molecular basis for the link between both entities and the underlying pathophysiology that results in insulin resistance and diabetes mellitus. We review the results of experimental and epidemiological studies, specifically examining the relationship between sleep duration and the immune and endocrine systems. PMID:21754974

  17. Visual discrimination learning under switching procedure in visually deprived cats.

    PubMed

    Zernicki, B

    1999-04-01

    Previous studies have shown that fine visual discrimination learning is severely impaired in cats binocularly deprived in the early period of life (BD cats) and also somewhat in control cats reared with open eyes in the limited laboratory environment (C cats) compared with cats reared in a normal rural environment (N cats). It was concluded that visual deprivation impairs perceptual learning. In the present study discriminative stimuli were dissimilar and so the task was perceptually easy, but using a switching procedure made it associatively difficult. In regular trials a gate with a grating pattern was positive and a blank gate negative, whereas in switching trials the meaning of the gates was reversed. The switching stimulus was intermittent light in some stages of training and intermittent tone in others. Learning was severely impaired in BD cats and somewhat in C cats and the deficit was similar under visual and auditory switching. Thus, early visual deprivation impairs associative learning. The impairment probably includes associations between switching stimulus and instrumental responses and configural associations between switching stimulus and discriminative stimuli. PMID:10212071

  18. Short-term visual deprivation improves the perception of harmonicity.

    PubMed

    Landry, Simon P; Shiller, Douglas M; Champoux, François

    2013-12-01

    Neuroimaging studies have shown that the perception of auditory stimuli involves occipital cortical regions traditionally associated with visual processing, even in the absence of any overt visual component to the task. Analogous behavioral evidence of an interaction between visual and auditory processing during purely auditory tasks comes from studies of short-term visual deprivation on the perception of auditory cues, however, the results of such studies remain equivocal. Although some data have suggested that visual deprivation significantly increases loudness and pitch discrimination and reduces spatial localization inaccuracies, it is still unclear whether such improvement extends to the perception of spectrally complex cues, such as those involved in speech and music perception. We present data demonstrating that a 90-min period of visual deprivation causes a transient improvement in the perception of harmonicity: a spectrally complex cue that plays a key role in music and speech perception. The results provide clear behavioral evidence supporting a role for the visual system in the processing of complex auditory stimuli, even in the absence of any visual component to the task. PMID:23957309

  19. Iron Deprivation Affects Drug Susceptibilities of Mycobacteria Targeting Membrane Integrity

    PubMed Central

    Pal, Rahul; Hameed, Saif; Fatima, Zeeshan

    2015-01-01

    Multidrug resistance (MDR) acquired by Mycobacterium tuberculosis (MTB) through continuous deployment of antitubercular drugs warrants immediate search for novel targets and mechanisms. The ability of MTB to sense and become accustomed to changes in the host is essential for survival and confers the basis of infection. A crucial condition that MTB must surmount is iron limitation, during the establishment of infection, since iron is required by both bacteria and humans. This study focuses on how iron deprivation affects drug susceptibilities of known anti-TB drugs in Mycobacterium smegmatis, a “surrogate of MTB.” We showed that iron deprivation leads to enhanced potency of most commonly used first line anti-TB drugs that could be reverted upon iron supplementation. We explored that membrane homeostasis is disrupted upon iron deprivation as revealed by enhanced membrane permeability and hypersensitivity to membrane perturbing agent leading to increased passive diffusion of drug and TEM images showing detectable differences in cell envelope thickness. Furthermore, iron seems to be indispensable to sustain genotoxic stress suggesting its possible role in DNA repair machinery. Taken together, we for the first time established a link between cellular iron and drug susceptibility of mycobacteria suggesting iron as novel determinant to combat MDR. PMID:26779346

  20. Regional Deprivation Index and Socioeconomic Inequalities Related to Infant Deaths in Korea

    PubMed Central

    2016-01-01

    Deprivation indices have been widely used to evaluate neighborhood socioeconomic status and therefore examine individuals within their regional context. Although some studies on the development of deprivation indices were conducted in Korea, additional research is needed to construct a more valid and reliable deprivation index. Therefore, a new deprivation index, named the K index, was constructed using principal component analysis. This index was compared with the Carstairs, Townsend and Choi indices. A possible association between infant death and deprivation was explored using the K index. The K index had a higher correlation with the infant mortality rate than did the other three indices. The regional deprivation quintiles were unequally distributed throughout the country. Despite the overall trend of gradually decreasing infant mortality rates, inequalities in infant deaths according to the deprivation quintiles persisted and widened. Despite its significance, the regional deprivation variable had a smaller effect on infant deaths than did individual variables. The K index functions as a deprivation index, and we may use this index to estimate the regional socioeconomic status in Korea. We found that inequalities in infant deaths according to the time trend persisted. To reduce the health inequalities among infants in Korea, regional deprivation should be considered. PMID:27051241

  1. Sleep deprivation impairs performance in the 5-choice continuous performance test: similarities between humans and mice.

    PubMed

    van Enkhuizen, Jordy; Acheson, Dean; Risbrough, Victoria; Drummond, Sean; Geyer, Mark A; Young, Jared W

    2014-03-15

    Several groups undergo extended periods without sleep due to working conditions or mental illness. Such sleep deprivation (SD) can deleteriously affect attentional processes and disrupt work and family functioning. Understanding the biological underpinnings of SD effects may assist in developing sleep therapies and cognitive enhancers. Utilizing cross-species tests of attentional processing in humans and rodents would aid in mechanistic studies examining SD-induced inattention. We assessed the effects of 36h of: (1) Total SD (TSD) in healthy male and female humans (n=50); and (2) REM SD (RSD) in male C57BL/6 mice (n=26) on performance in the cross-species 5-choice continuous performance test (5C-CPT). The 5C-CPT includes target trials on which subjects were required to respond and non-target trials on which subjects were required to inhibit from responding. TSD-induced effects on human psychomotor vigilance test (PVT) were also examined. Effects of SD were also examined on mice split into good and poor performance groups based on pre-deprivation scores. In the human 5C-CPT, TSD decreased hit rate and vigilance with trend-level effects on accuracy. In the PVT, TSD slowed response times and increased lapses. In the mouse 5C-CPT, RSD reduced accuracy and hit rate with trend-level effects on vigilance, primarily in good performers. In conclusion, SD induced impaired 5C-CPT performance in both humans and mice and validates the 5C-CPT as a cross-species translational task. The 5C-CPT can be used to examine mechanisms underlying SD-induced deficits in vigilance and assist in testing putative cognitive enhancers. PMID:24333377

  2. Belief about Nicotine Modulates Subjective Craving and Insula Activity in Deprived Smokers

    PubMed Central

    Gu, Xiaosi; Lohrenz, Terry; Salas, Ramiro; Baldwin, Philip R.; Soltani, Alireza; Kirk, Ulrich; Cinciripini, Paul M.; Montague, P. Read

    2016-01-01

    Little is known about the specific neural mechanisms through which cognitive factors influence craving and associated brain responses, despite the initial success of cognitive therapies in treating drug addiction. In this study, we investigated how cognitive factors such as beliefs influence subjective craving and neural activities in nicotine-addicted individuals using model-based functional magnetic resonance imaging (fMRI) and neuropharmacology. Deprived smokers (N = 24) participated in a two-by-two balanced placebo design, which crossed beliefs about nicotine (told “nicotine” vs. told “no nicotine”) with the nicotine content in a cigarette (nicotine vs. placebo) which participants smoked immediately before performing a fMRI task involving reward learning. Subjects’ reported craving was measured both before smoking and after the fMRI session. We found that first, in the presence of nicotine, smokers demonstrated significantly reduced craving after smoking when told “nicotine in cigarette” but showed no change in craving when told “no nicotine.” Second, neural activity in the insular cortex related to craving was only significant when smokers were told “nicotine” but not when told “no nicotine.” Both effects were absent in the placebo condition. Third, insula activation related to computational learning signals was modulated by belief about nicotine regardless of nicotine’s presence. These results suggest that belief about nicotine has a strong impact on subjective craving and insula responses related to both craving and learning in deprived smokers, providing insights into the complex nature of belief–drug interactions. PMID:27468271

  3. The Response to Visual Form Deprivation Differs with Age in Marmosets

    PubMed Central

    Troilo, David; Nickla, Debora L.

    2007-01-01

    Purpose To characterize the effects of visual form deprivation by diffuser in marmoset monkey eyes across a range of ages. Methods Twenty-four common marmosets were grouped by onset of deprivation (group 1: 0-39 days, n = 6; group 2: 40-99 days, n = 10; and group 3: 100-200 days, n = 8). Monocular form deprivation was induced with a white translucent diffuser worn for 28 to 88 days (mean durations: group 1, 32 days; group 2, 56 days; and group 3, 51 days). Refractive state, corneal curvature, and vitreous chamber depth were measured after cycloplegia. Both experimental and control eyes were measured multiple times before, during, and after the visual deprivation period. Results Marmosets in all age groups tested were susceptible to visual form deprivation myopia; however, the response to form deprivation was variable and included a majority with axial myopia (n = 15), several nonresponders (n = 4), a single late responder (axial myopia after the end of deprivation period), and several axial hyperopes (n = 4). For all animals that responded with axial myopia, the increase in vitreous chamber depth and myopia was inversely proportional to the age of onset of deprivation (ANOVA, P < 0.05). After the end of the period of deprivation, recovery from myopia by reduction of the axial growth rate was observed in three animals from group 1 and three animals from group 2. Conclusions Form deprivation by diffusers disrupted emmetropization in marmosets over a range of ages. The responses varied among individuals and with age, suggesting that the maturity of the eye may influence the response to visual signals responsible for form deprivation myopia and perhaps emmetropization. Recovery from diffuser-induced form deprivation myopia was apparent in some animals, in contrast to that reported for visual deprivation by lid-suturing, and appears more prevalent in the younger animals. PMID:15914598

  4. Analysis of the Physiological and Molecular Responses of Dunaliella salina to Macronutrient Deprivation

    PubMed Central

    Lv, Hexin; Cui, Xianggan; Wahid, Fazli; Xia, Feng; Zhong, Cheng; Jia, Shiru

    2016-01-01

    The halotolerant chlorophyte Dunaliella salina can accumulate up to 10% of its dry weight as β-carotene in chloroplasts when subjected to adverse conditions, including nutrient deprivation. However, the mechanisms of carotenoid biosynthesis are poorly understood. Here, the physiological and molecular responses to the deprivation of nitrogen (-N), sulfur (-S), phosphorus (-P) and different combinations of those nutrients (-N-P, -N-S, -P-S and -N-P-S) were compared to gain insights into the underlying regulatory mechanisms of carotenoid biosynthesis. The results showed that both the growth and photosynthetic rates of cells were decreased during nutrient deprivation, accompanied by lipid globule accumulation and reduced chlorophyll levels. The SOD and CAT activities of the cells were altered during nutrient deprivation, but their responses were different. The total carotenoid contents of cells subjected to multiple nutrient deprivation were higher than those of cells subjected to single nutrient deprivation and non-stressed cells. The β-carotene contents of cells subjected to -N-P, -N-S and -N-P-S were higher than those of cells subjected to single nutrient deprivation. Cells subjected to sulfur deprivation accumulated more lutein than cells subjected to nitrogen and phosphorous deprivation. In contrast, no cumulative effects of nutrient deprivation on the transcription of genes in the carotenogenic pathway were observed because MEP and carotenogenic pathway genes were up-regulated during single nutrient deprivation but were downregulated during multiple nutrient deprivation. Therefore, we proposed that the carotenoid biosynthesis pathway of D. salina is regulated at both the transcriptional and posttranscriptional levels and that a complex crosstalk occurs at the physiological and molecular levels in response to the deprivation of different nutrients. PMID:27023397

  5. Analysis of the Physiological and Molecular Responses of Dunaliella salina to Macronutrient Deprivation.

    PubMed

    Lv, Hexin; Cui, Xianggan; Wahid, Fazli; Xia, Feng; Zhong, Cheng; Jia, Shiru

    2016-01-01

    The halotolerant chlorophyte Dunaliella salina can accumulate up to 10% of its dry weight as β-carotene in chloroplasts when subjected to adverse conditions, including nutrient deprivation. However, the mechanisms of carotenoid biosynthesis are poorly understood. Here, the physiological and molecular responses to the deprivation of nitrogen (-N), sulfur (-S), phosphorus (-P) and different combinations of those nutrients (-N-P, -N-S, -P-S and -N-P-S) were compared to gain insights into the underlying regulatory mechanisms of carotenoid biosynthesis. The results showed that both the growth and photosynthetic rates of cells were decreased during nutrient deprivation, accompanied by lipid globule accumulation and reduced chlorophyll levels. The SOD and CAT activities of the cells were altered during nutrient deprivation, but their responses were different. The total carotenoid contents of cells subjected to multiple nutrient deprivation were higher than those of cells subjected to single nutrient deprivation and non-stressed cells. The β-carotene contents of cells subjected to -N-P, -N-S and -N-P-S were higher than those of cells subjected to single nutrient deprivation. Cells subjected to sulfur deprivation accumulated more lutein than cells subjected to nitrogen and phosphorous deprivation. In contrast, no cumulative effects of nutrient deprivation on the transcription of genes in the carotenogenic pathway were observed because MEP and carotenogenic pathway genes were up-regulated during single nutrient deprivation but were downregulated during multiple nutrient deprivation. Therefore, we proposed that the carotenoid biosynthesis pathway of D. salina is regulated at both the transcriptional and posttranscriptional levels and that a complex crosstalk occurs at the physiological and molecular levels in response to the deprivation of different nutrients. PMID:27023397

  6. Androgen deprivation of prostate cancer: Leading to a therapeutic dead end.

    PubMed

    Katzenwadel, Arndt; Wolf, Philipp

    2015-10-10

    Androgen deprivation therapy (ADT) is considered as the standard therapy for men with de novo or recurrent metastatic prostate cancer. ADT commonly leads to initial biochemical and clinical responses. However, several months after the beginning of treatment, tumors become castration-resistant and virtually all patients show disease progression. At this stage, tumors are no longer curable and cancer treatment options are only palliative. In this review, we describe molecular alterations in tumor cells during ADT, which lead to deregulation of different signaling pathways and castration-resistance, and how they might interfere with the clinical outcome of different second-line therapeutics. A recent breakthrough finding that early chemotherapy is associated with a significant survival benefit in metastatic hormone-sensitive disease highlights the fact that there is time for a fundamental paradigm shift in the treatment of advanced prostate cancer. Therapeutic intervention seems to be indicated before a castration-resistant stage is reached to improve therapeutic outcome and to reduce undesirable side effects. PMID:26185001

  7. The effect of total sleep deprivation on cognitive functions in normal adult male subjects.

    PubMed

    Kim, D J; Lee, H P; Kim, M S; Park, Y J; Go, H J; Kim, K S; Lee, S P; Chae, J H; Lee, C T

    2001-07-01

    This study was conducted to evaluate the effect of acute sleep deprivation on cognitive functions. A total of 18 healthy right handed males were deprived of sleep for 24 hours. Luria-Nebraska Neuropsychological Battery and calculation & digit-span subtest of K-WAIS were administered before and after sleep deprivation in order to examine the changes of cognitive functions. There were no differences in freedom from distractibility, tacile function, visual function, reading, writing, arithmetic and intellectual process function. However, the cognitive functions such as motor, rhythm, receptive & expressive speech, memory and complex verbal arithmetic function were decreased after sleep deprivation. All of these functions are known to be related to the right anterior hemisphere. For localization scales, the scores of right frontal and right temporal dysfunction scale were increased after sleep deprivation. These results indicate that sleep deprivation has a negative effect on cognitive functions, especially those associated with right anterior hemisphere or subcortical areas. PMID:11699337

  8. Food deprivation and emotional reactions to food cues: implications for eating disorders.

    PubMed

    Drobes, D J; Miller, E J; Hillman, C H; Bradley, M M; Cuthbert, B N; Lang, P J

    2001-01-01

    Two studies examined emotional responding to food cues. In experiment 1, normal college students were assigned to 0-, 6- or 24-h of food deprivation prior to presentations of standard emotional and food-related pictures. Food deprivation had no impact on responses elicited by standard emotional pictures. However, subjective and psychophysiological reactions to food pictures were affected significantly by deprivation. Importantly, food-deprived subjects viewing food pictures showed an enhanced startle reflex and increased heart rate. Experiment 2 replicated the food deprivation effects from experiment 1, and examined participants reporting either a habitual pattern of restrained (anorexia-like) or binge (bulimia-like) eating. Food-deprived and binge eater groups showed startle potentiation to food cues, and rated these stimuli as more pleasant, relative to restrained eaters and control subjects. The results are interpreted from the perspective that startle modulation reflects activation of defensive or appetitive motivation. Implications of the data for understanding eating disorders are considered. PMID:11454438

  9. Site Specific Activation of AKT Protects Cells from Death Induced by Glucose Deprivation

    PubMed Central

    Gao, Meng; Liang, Jiyong; Lu, Yiling; Guo, Huifang; German, Peter; Bai, Shanshan; Jonasch, Eric; Yang, Xingsheng; Mills, Gordon B.; Ding, Zhiyong

    2013-01-01

    The serine/threonine kinase AKT is a key mediator of cancer cell survival. We demonstrate that transient glucose deprivation modestly induces AKT phosphorylation at both Thr308 and Ser473. In contrast, prolonged glucose deprivation induces selective AKTThr308 phosphorylation and phosphorylation of a distinct subset of AKT downstream targets leading to cell survival under metabolic stress. Glucose deprivation-induced AKTThr308 phosphorylation is dependent on PDK1 and PI3K but not EGFR or IGF1R. Prolonged glucose deprivation induces the formation of a complex of AKT, PDK1, and the GRP78 chaperone protein, directing phosphorylation of AKTThr308 but AKTSer473. Our results reveal a novel mechanism of AKT activation under prolonged glucose deprivation that protects cells from metabolic stress. The selective activation of AKTThr308 phosphorylation that occurs during prolonged nutrient deprivation may provide an unexpected opportunity for the development and implementation of drugs targeting cell metabolism and aberrant AKT signaling. PMID:23396361

  10. The dual effect of paradoxical sleep deprivation on murine immune functions.

    PubMed

    Sá-Nunes, Anderson; Bizzarro, Bruna; Egydio, Flávia; Barros, Michele S; Sesti-Costa, Renata; Soares, Elyara M; Pina, Adriana; Russo, Momtchilo; Faccioli, Lúcia H; Tufik, Sergio; Andersen, Monica L

    2016-01-15

    We aimed to evaluate the effect of paradoxical sleep deprivation on the cellular migration during inflammation, the peritoneal macrophage phenotype and the infectious stimulus outcomes. A/J mice were inoculated with thioglycollate and exposed to paradoxical sleep deprivation. Sleep-deprived animals presented decreased cell migration compared to controls. Nitric oxide production was reduced in macrophages from sleep-deprived mice compared to controls. Cell surface analysis showed that sleep deprivation reduced F4/80(+)/CD80(low) peritoneal cell population induced by thioglycollate injection. Sleep-deprived mice were not more susceptible to infection than control mice. Our findings challenge the general perception that sleep loss always increases infection susceptibility. PMID:26711562

  11. How sleep deprivation affects psychological variables related to college students' cognitive performance.

    PubMed

    Pilcher, J J; Walters, A S

    1997-11-01

    The effects of sleep deprivation on cognitive performance psychological variables related to cognitive performance were studied in 44 college students. Participants completed the Watson-Glaser Critical Thinking Appraisal after either 24 hours of sleep deprivation or approximately 8 hours of sleep. After completing the cognitive task, the participants completed 2 questionnaires, one assessing self-reported effort, concentration, and estimated performance, the other assessing off-task cognitions. As expected, sleep-deprived participants performed significantly worse than the nondeprived participants on the cognitive task. However, the sleep-deprived participants rated their concentration and effort higher than the nondeprived participants did. In addition, the sleep-deprived participants rated their estimated performance significantly higher than the nondeprived participants did. The findings indicate that college students are not aware of the extent to which sleep deprivation negatively affects their ability to complete cognitive tasks. PMID:9394089

  12. The effects of food deprivation and incentive motivation on blood glucose levels and cognitive function.

    PubMed

    Green, M W; Elliman, N A; Rogers, P J

    1997-11-01

    The current study investigated the relationships between blood glucose levels, mild food deprivation, sympathetic arousal, and cognitive processing efficiency. Subjects (n = 82) were randomly assigned to four experimental conditions, comprising combined manipulations of food deprivation and incentive motivation. Baseline and mid-session measurements of blood glucose, blood pressure and pulse rate were taken. Subjects completed a number of measures of cognitive processing efficiency and self report measures of affective and somatic state. Although glucose levels were lowered following food deprivation, there was no significant detrimental effect of food deprivation on task performance. However, improved recognition memory processing times were associated with deprivation. Incentive motivation was associated with faster simple reaction times and higher diastolic blood pressure. There were no significant relationships between glucose levels and task performance, further supporting the hypothesis that the brain is relatively invulnerable to short food deprivation. PMID:9399371

  13. Prognostic Value of Abnormal p53 Expression in Locally Advanced Prostate Cancer Treated With Androgen Deprivation and Radiotherapy: A Study Based on RTOG 9202

    SciTech Connect

    Che Mingxin DeSilvio, Michelle; Pollack, Alan; Grignon, David J.; Venkatesan, Varagur Mohan; Hanks, Gerald E.; Sandler, Howard M.

    2007-11-15

    Purpose: The goal of this study was to verify the significance of p53 as a prognostic factor in Radiation Therapy Oncology Group 9202, which compared short-term androgen deprivation (STAD) with radiation therapy (RT) to long-term androgen deprivation + RT in men with locally advanced prostate cancer (Pca). Methods and Materials: Tumor tissue was sufficient for p53 analysis in 777 cases. p53 status was determined by immunohistochemistry. Abnormal p53 expression was defined as 20% or more tumor cells with positive nuclei. Univariate and multivariate Cox proportional hazards models were used to evaluate the relationships of p53 status to patient outcomes. Results: Abnormal p53 was detected in 168 of 777 (21.6%) cases, and was significantly associated with cause-specific mortality (adjusted hazard ratio [HR] = 1.89; 95% confidence interval (CI) 1.14 - 3.14; p = 0.014) and distant metastasis (adjusted HR = 1.72; 95% CI 1.13-2.62; p = 0.013). When patients were divided into subgroups according to assigned treatment, only the subgroup of patients who underwent STAD + RT showed significant correlation between p53 status and cause-specific mortality (adjusted HR = 2.43; 95% CI = 1.32-4.49; p = 0.0044). When patients were divided into subgroups according to p53 status, only the subgroup of patients with abnormal p53 showed significant association between assigned treatment and cause-specific mortality (adjusted HR = 3.81; 95% CI 1.40-10.37; p = 0.0087). Conclusions: Abnormal p53 is a significant prognostic factor for patients with prostate cancer who undergo short-term androgen deprivation and radiotherapy. Long-term androgen deprivation may significantly improve the cause-specific survival for those with abnormal p53.

  14. Neighbourhood fast food environment and area deprivation-substitution or concentration?

    PubMed

    Macdonald, Laura; Cummins, Steven; Macintyre, Sally

    2007-07-01

    It has been hypothesised that deprived neighbourhoods have poorer quality food environments which may promote the development of obesity. We investigated associations between area deprivation and the location of the four largest fast-food chains in Scotland and England. We found statistically significant increases in density of outlets from more affluent to more deprived areas for each individual fast-food chain and all chains combined. These results provide support for a 'concentration' effect whereby plausible health-damaging environmental risk factors for obesity appear to be 'concentrated' in more deprived areas of England and Scotland. PMID:17189662

  15. Effects of paradoxical sleep deprivation on the performance of rats in a model of visual attention.

    PubMed

    Godoi, Francisco Rafael do Lago; Oliveira, Maria Gabriela Menezes; Tufik, Sergio

    2005-11-30

    In the present work we sought to evaluate the effects of paradoxical sleep deprivation (PSD) on the performance of rats in the five-choice serial reaction time task, a test designed to assess attentional function. Adult male Wistar rats were trained to detect a brief (1 s) light stimulus randomly presented in one of five locations in a box specially designed for the task. After achieving stable performance, the animals were submitted to 96 h of sleep deprivation by the platform technique, in which the rats are placed on top of small platforms in a tank filled with water. During sleep, particularly during the paradoxical stage, the loss of muscle tone make the animals fall into the water, thus awakening them and so depriving of sleep. Performance in the task was assessed daily during the 96 h deprivation period and also during seven recovery days afterwards. Paradoxical sleep deprivation reduced accuracy on the on the third (72 h) and fourth (96 h) days of sleep deprivation compared to home-cage controls, and this impairment reverted soon after the beginning of the recovery period. Sleep-deprived animals also showed an increase in omissions in the first day of PSD and a reduction on the number of trials started on the fourth day of sleep deprivation. No significant group differences were observed in premature and perseverative responses, correct response latency and reward latency. Our results thus indicate that paradoxical sleep deprivation impairs attentional function. PMID:16111775

  16. Unsupervised Online Classifier in Sleep Scoring for Sleep Deprivation Studies

    PubMed Central

    Libourel, Paul-Antoine; Corneyllie, Alexandra; Luppi, Pierre-Hervé; Chouvet, Guy; Gervasoni, Damien

    2015-01-01

    Study Objective: This study was designed to evaluate an unsupervised adaptive algorithm for real-time detection of sleep and wake states in rodents. Design: We designed a Bayesian classifier that automatically extracts electroencephalogram (EEG) and electromyogram (EMG) features and categorizes non-overlapping 5-s epochs into one of the three major sleep and wake states without any human supervision. This sleep-scoring algorithm is coupled online with a new device to perform selective paradoxical sleep deprivation (PSD). Settings: Controlled laboratory settings for chronic polygraphic sleep recordings and selective PSD. Participants: Ten adult Sprague-Dawley rats instrumented for chronic polysomnographic recordings Measurements: The performance of the algorithm is evaluated by comparison with the score obtained by a human expert reader. Online detection of PS is then validated with a PSD protocol with duration of 72 hours. Results: Our algorithm gave a high concordance with human scoring with an average κ coefficient > 70%. Notably, the specificity to detect PS reached 92%. Selective PSD using real-time detection of PS strongly reduced PS amounts, leaving only brief PS bouts necessary for the detection of PS in EEG and EMG signals (4.7 ± 0.7% over 72 h, versus 8.9 ± 0.5% in baseline), and was followed by a significant PS rebound (23.3 ± 3.3% over 150 minutes). Conclusions: Our fully unsupervised data-driven algorithm overcomes some limitations of the other automated methods such as the selection of representative descriptors or threshold settings. When used online and coupled with our sleep deprivation device, it represents a better option for selective PSD than other methods like the tedious gentle handling or the platform method. Citation: Libourel PA, Corneyllie A, Luppi PH, Chouvet G, Gervasoni D. Unsupervised online classifier in sleep scoring for sleep deprivation studies. SLEEP 2015;38(5):815–828. PMID:25325478

  17. Creatine supplementation, sleep deprivation, cortisol, melatonin and behavior.

    PubMed

    McMorris, T; Harris, R C; Howard, A N; Langridge, G; Hall, B; Corbett, J; Dicks, M; Hodgson, C

    2007-01-30

    The effect of creatine supplementation and sleep deprivation, with intermittent moderate-intensity exercise, on cognitive and psychomotor performance, mood state, effort and salivary concentrations of cortisol and melatonin were examined. Subjects were divided into a creatine supplementation group and a placebo group. They took 5 g of creatine monohydrate or a placebo, dependent on their group, four times a day for 7 days immediately prior to the experiment. They undertook tests examining central executive functioning, short-term memory, choice reaction time, balance, mood state and effort at baseline and following 18-, 24- and 36-h sleep deprivation, with moderate intermittent exercise. Saliva samples were taken prior to each set of tests. A group x time analysis of covariance, with baseline performance the covariate, showed that the creatine group performed significantly (p < 0.05) better than the placebo group on the central executive task but only at 36 h. The creatine group demonstrated a significant (p < 0.01) linear improvement in performance of the central executive task throughout the experiment, while the placebo group showed no significant effects. There were no significant differences between the groups for any of the other variables. A significant (p < 0.001) main effect of time was found for the balance test with a linear improvement being registered. Cortisol concentrations on Day 1 were significantly (p < 0.01) higher than on Day 2. Mood significantly (p < 0.001) deteriorated up to 24 h with no change from 24 to 36 h. Effort at baseline was significantly (p < 0.01) lower than in the other conditions. It was concluded that, during sleep deprivation with moderate-intensity exercise, creatine supplementation only affects performance of complex central executive tasks. PMID:17046034

  18. Auditory, tactile, and audiotactile information processing following visual deprivation.

    PubMed

    Occelli, Valeria; Spence, Charles; Zampini, Massimiliano

    2013-01-01

    We highlight the results of those studies that have investigated the plastic reorganization processes that occur within the human brain as a consequence of visual deprivation, as well as how these processes give rise to behaviorally observable changes in the perceptual processing of auditory and tactile information. We review the evidence showing that visual deprivation affects the establishment of the spatial coordinate systems involved in the processing of auditory and tactile inputs within the peripersonal space around an individual. In blind individuals, the absence of a conjoint activation of external coordinate systems across modalities co-occurs with a higher capacity to direct auditory and tactile attentional resources to different spatial locations and to ignore irrelevant distractors. Both processes could thus contribute to the reduced spatial multisensory binding that has been observed in those who are blind. The interplay between auditory and tactile information in visually deprived individuals is modulated by attentional factors. Blind individuals typically outperform sighted people in those tasks where the target is presented in one sensory modality (and the other modality acts as a distractor). By contrast, they are less efficient in tasks explicitly requiring the combination of information across sensory modalities. The review highlights how these behavioral effects are subserved by extensive plastic changes at the neural level, with brain areas traditionally involved in visual functioning switching and being recruited for the processing of stimuli within the intact residual senses. We also discuss the roles played by other intervening factors with regard to compensatory mechanisms, such as previous visual experience, age at onset of blindness, and learning effects. PMID:22612281

  19. Testosterone deprivation accelerates cardiac dysfunction in obese male rats.

    PubMed

    Pongkan, Wanpitak; Pintana, Hiranya; Sivasinprasasn, Sivaporn; Jaiwongkam, Thidarat; Chattipakorn, Siriporn C; Chattipakorn, Nipon

    2016-06-01

    Low testosterone level is associated with increased risks of cardiovascular diseases. As obese-insulin-resistant condition could impair cardiac function and that the incidence of obesity is increased in aging men, a condition of testosterone deprivation could aggravate the cardiac dysfunction in obese-insulin-resistant subjects. However, the mechanism underlying this adverse effect is unclear. This study investigated the effects of obesity on metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function in testosterone-deprived rats. Orchiectomized or sham-operated male Wistar rats (n=36per group) were randomly divided into groups and were given either a normal diet (ND, 19.77% of energy fat) or a high-fat diet (HFD, 57.60% of energy fat) for 12weeks. Metabolic parameters, HRV, LV function, and cardiac mitochondrial function were determined at 4, 8, and 12weeks after starting each feeding program. We found that insulin resistance was observed after 8weeks of the consumption of a HFD in both sham (HFS) and orchiectomized (HFO) rats. Neither the ND sham (NDS) group nor ND orchiectomized (NDO) rats developed insulin resistance. The development of depressed HRV, LV contractile dysfunction, and increased cardiac mitochondrial reactive oxygen species production was observed earlier in orchiectomized (NDO and HFO) rats at week 4, whereas HFS rats exhibited these impairments later at week 8. These findings suggest that testosterone deprivation accelerates the impairment of cardiac autonomic regulation and LV function via increased oxidative stress and impaired cardiac mitochondrial function in obese-orchiectomized male rats. PMID:27000685

  20. Sleep deprivation affects inflammatory marker expression in adipose tissue

    PubMed Central

    2010-01-01

    Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation. Methods The study consisted of two groups: a control (C) group and a paradoxical sleep deprivation by 96 h (PSD) group. Ten rats were randomly assigned to either the control group (C) or the PSD. Mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissue, liver and serum were collected following completion of the PSD protocol. Levels of interleukin (IL)-6, interleukin (IL)-10 and tumour necrosis factor (TNF)-α were analysed in MEAT and RPAT, and leptin, adiponectin, glucose, corticosterone and lipid profile levels were analysed in serum. Results IL-6 levels were elevated in RPAT but remained unchanged in MEAT after PSD. IL-10 protein concentration was not altered in either depot, and TNF-α levels decreased in MEAT. Glucose, triglycerides (TG), VLDL and leptin decreased in serum after 96 hours of PSD; adiponectin was not altered and corticosterone was increased. Conclusion PSD decreased fat mass and may modulate the cytokine content in different depots of adipose tissue. The inflammatory response was diminished in both depots of adipose tissue, with increased IL-6 levels in RPAT and decreased TNF-α protein concentrations in MEAT and increased levels of corticosterone in serum. PMID:21034496

  1. Sleep Deficiency and Deprivation Leading to Cardiovascular Disease

    PubMed Central

    Kohansieh, Michelle; Makaryus, Amgad N.

    2015-01-01

    Sleep plays a vital role in an individual's mental, emotional, and physiological well-being. Not only does sleep deficiency lead to neurological and psychological disorders, but also the literature has explored the adverse effects of sleep deficiency on the cardiovascular system. Decreased quantity and quality of sleep have been linked to cardiovascular disease (CVD) risk factors, such as hypertension, obesity, diabetes, and dyslipidemia. We explore the literature correlating primary sleep deficiency and deprivation as a cause for cardiovascular disease and cite endothelial dysfunction as a common underlying mechanism. PMID:26495139

  2. The molecular neurobiology of the sleep-deprived, fuzzy brain.

    PubMed

    Sweatt, J David; Hawkins, Kimberly E

    2016-01-01

    Sleep deprivation is well established to cause diminution of cognitive function, including disruption of both minute-to-minute working memory and decrements in the stabilization of long-term memories. Moreover, "replay" during sleep of episodes and sequences of events that were experienced during wakefulness has been implicated in consolidation of long-term memories. However, the molecular mechanisms underlying the role of sleep in memory function are just starting to be defined. In this issue of Science Signaling, Tudor et al identify one molecular component underlying the effects of sleep on memory function: dynamic experience-dependent regulation of protein synthesis in the hippocampus. PMID:27117249

  3. Sleep deprivation and the organization of the behavioral states.

    NASA Technical Reports Server (NTRS)

    Dement, W. C.

    1972-01-01

    Questions concerning the significance of sleep in the developing organism are investigated, together with the mechanisms that underlie the unique distribution of behavioral states at any particular age and during any particular experimental manipulation. It is attempted to define the states of sleep and wakefulness in terms of a temporal confluence of a number of more or less independent processes, taking also into account the functional consequences of these attributes. The results of a selective deprivation of rapid eye movement sleep are explored, giving attention to effects on sleep, behavioral changes, brain excitability, pharmacological changes, and biochemical changes.

  4. Effects of 6-hydroxydopamine on visual deprivation in the kitten striate cortex.

    PubMed

    Daw, N W; Rader, R K; Robertson, T W; Ariel, M

    1983-05-01

    We tested the effects of 6-hydroxydopamine (6-OHDA) on two forms of visual deprivation--monocular and directional deprivation. In normal kittens monocular deprivation leads to a change in the ocular dominance histogram recorded from the visual cortex, and directional deprivation leads to a change in the percentage of directionally sensitive cells responding to the appropriate direction of movement. 6-OHDA was infused into the occipital cortex prior to the peak of the critical period for the effects of visual deprivation. In agreement with the results of Kasamatsu et al. (Kasamatsu, T., and J. D. Pettigrew (1979) J. Comp. Neurol. 185: 139-162; Kasamatsu, T., J. D. Pettigrew, and M. Ary (1979) J. Comp. Neurol. 185: 163-182), suture of one eye (monocular deprivation) after the 6-OHDA treatment did not lead to a shift in ocular dominance in the area of striate cortex infused. Moreover, rearing kittens in an environment continually moving past them in one direction (directional deprivation) did not lead to a change in the percentage of cells preferring movement in that direction. In both rearing procedures the 6-OHDA did not make the cells in the cortex nonspecific, compared to cells recorded from the cortex of animals reared similarly but without infusion of 6-OHDA. Monocular and directional deprivation are forms of visual deprivation with different critical periods, probably involving different synapses. Therefore, the effect of 6-OHDA on visual deprivation is a general one, involving more than one kind of visual deprivation. In both cases 6-OHDA abolishes the plasticity of the visual cortex. PMID:6405018

  5. Cumulative disadvantage? Exploring relationships between neighbourhood deprivation trends (1991 to 2006) and mortality in New Zealand

    PubMed Central

    2013-01-01

    Background Area-level socioeconomic deprivation has been shown to exert an independent effect on both individual and population health outcomes and health-related behaviours. Evidence also suggests that health and economic inequalities in many countries are increasing in some areas but may be on the decline in others. While area-level deprivation at a single point in time is known to influence health, the literature relating to longitudinal deprivation of communities and associated health impacts is sparse. This research makes a methodological contribution to this literature. Methods Using a Latent Class Growth Model, we identified 12 deprivation trends (1991–2006) for small areas (n = 1621) in New Zealand. We then fitted regression models to assess the effects of trends of relative deprivation on a) all-cause mortality, and b) cardiovascular mortality (2005–2007) by census area unit. For comparison, we also fitted regression models to assess the effect of deprivation deciles (in 2006) on outcomes a) and b). Results Using trends, we found a positive association between deprivation and mortality, except for two trends for both all-cause and CVD-related mortality. When comparing trends and deciles of deprivation, we observed similar patterns. However, we found that AIC values were slightly lower for the model including deciles, indicating better model fit. Conclusion While we found that current deprivation was a slightly better predictor of mortality, the approach used here offers a potentially useful alternative. Future deprivation research must consider the possible loss of information about health benefits of living in areas where relative deprivation has improved in cross-sectional analyses. PMID:23964568

  6. Sustainable Hydrogen Photoproduction by Phosphorus-Deprived Marine Green Microalgae Chlorella sp.

    PubMed Central

    Batyrova, Khorcheska; Gavrisheva, Anastasia; Ivanova, Elena; Liu, Jianguo; Tsygankov, Anatoly

    2015-01-01

    Previously it has been shown that green microalga Chlamydomonas reinhardtii is capable of prolonged H2 photoproduction when deprived of sulfur. In addition to sulfur deprivation (-S), sustained H2 photoproduction in C. reinhardtii cultures can be achieved under phosphorus-deprived (-P) conditions. Similar to sulfur deprivation, phosphorus deprivation limits O2 evolving activity in algal cells and causes other metabolic changes that are favorable for H2 photoproduction. Although significant advances in H2 photoproduction have recently been realized in fresh water microalgae, relatively few studies have focused on H2 production in marine green microalgae. In the present study phosphorus deprivation was applied for hydrogen production in marine green microalgae Chlorella sp., where sulfur deprivation is impossible due to a high concentration of sulfates in the sea water. Since resources of fresh water on earth are limited, the possibility of hydrogen production in seawater is more attractive. In order to achieve H2 photoproduction in P-deprived marine green microalgae Chlorella sp., the dilution approach was applied. Cultures diluted to about 0.5–1.8 mg Chl·L−1 in the beginning of P-deprivation were able to establish anaerobiosis, after the initial growth period, where cells utilize intracellular phosphorus, with subsequent transition to H2 photoproduction stage. It appears that marine microalgae during P-deprivation passed the same stages of adaptation as fresh water microalgae. The presence of inorganic carbon was essential for starch accumulation and subsequent hydrogen production by microalgae. The H2 accumulation was up to 40 mL H2 gas per 1iter of the culture, which is comparable to that obtained in P-deprived C. reinhardtii culture. PMID:25629229

  7. Sustainable hydrogen photoproduction by phosphorus-deprived marine green microalgae Chlorella sp.

    PubMed

    Batyrova, Khorcheska; Gavrisheva, Anastasia; Ivanova, Elena; Liu, Jianguo; Tsygankov, Anatoly

    2015-01-01

    Previously it has been shown that green microalga Chlamydomonas reinhardtii is capable of prolonged H2 photoproduction when deprived of sulfur. In addition to sulfur deprivation (-S), sustained H2 photoproduction in C. reinhardtii cultures can be achieved under phosphorus-deprived (-P) conditions. Similar to sulfur deprivation, phosphorus deprivation limits O2 evolving activity in algal cells and causes other metabolic changes that are favorable for H2 photoproduction. Although significant advances in H2 photoproduction have recently been realized in fresh water microalgae, relatively few studies have focused on H2 production in marine green microalgae. In the present study phosphorus deprivation was applied for hydrogen production in marine green microalgae Chlorella sp., where sulfur deprivation is impossible due to a high concentration of sulfates in the sea water. Since resources of fresh water on earth are limited, the possibility of hydrogen production in seawater is more attractive. In order to achieve H2 photoproduction in P-deprived marine green microalgae Chlorella sp., the dilution approach was applied. Cultures diluted to about 0.5-1.8 mg Chl·L-1 in the beginning of P-deprivation were able to establish anaerobiosis, after the initial growth period, where cells utilize intracellular phosphorus, with subsequent transition to H2 photoproduction stage. It appears that marine microalgae during P-deprivation passed the same stages of adaptation as fresh water microalgae. The presence of inorganic carbon was essential for starch accumulation and subsequent hydrogen production by microalgae. The H2 accumulation was up to 40 mL H2 gas per 1iter of the culture, which is comparable to that obtained in P-deprived C. reinhardtii culture. PMID:25629229

  8. Effect of Social Deprivation on the Stage and Mode of Presentation of Colorectal Cancer

    PubMed Central

    Ashford-Wilson, Sarah; Brown, Stephanie; Pal, Atanu; Lal, Roshan; Aryal, Kamal

    2016-01-01

    Purpose Based in a hospital serving one of the most deprived areas in the United Kingdom (UK), we aimed to investigate, using the Indices of Deprivation 2010, the hypothesis that deprivation affects the stage and mode of presentation of colorectal cancer. Methods All newly diagnosed patients with colorectal cancer presenting to a District General Hospital in the UK between January 2010 and December 2014 were included. Data were collected from the Somerset National Cancer Database. The effect of social deprivation, measured using the Index of Multiple Deprivation Score, on the stage and mode of presentation was evaluated utilizing Microsoft Excel and IBM SPSS ver. 22.0. Results A total of 701 patients (54.5% male; mean age, 76 years) were included; 534 (76.2%) underwent a surgical procedure, and 497 (70.9%) underwent a colorectal resection. Of the patients undergoing a colorectal resection, 86 (17.3%) had an emergency surgical resection. Social deprivation was associated with Duke staging (P = 0.09). The 90-day mortality in patients undergoing emergency surgery was 12.8% compared to 6.8% in patients undergoing elective surgery (P = 0.06). No association was found between deprivation and emergency presentation (P = 0.97). A logistic regression analysis showed no increase in the probability of metastasis amongst deprived patients. Conclusion This study suggests an association between deprivation and the stage of presentation of colorectal cancer. Patients undergoing emergency surgery tend to have a higher 90-day mortality rate, although this was not related to deprivation. This study highlights the need to develop an individual measure to assess social deprivation. PMID:27626022

  9. DT-13, a saponin monomer of dwarf lilyturf tuber, induces autophagy and potentiates anti-cancer effect of nutrient deprivation.

    PubMed

    Li, Hongyang; Sun, Li; de Carvalho, Evandro Lopes; Li, Xinxin; Lv, Xiaodan; Khan, Ghulam Jilany; Semukunzi, Herve; Yuan, Shengtao; Lin, Sensen

    2016-06-15

    Metabolic stress induces autophagy as a protective mechanism in tumorigenesis and development. Conversely, excessive autophagy in nutrient-deprived cancer cells would be beneficial for cancer therapy. DT-13, the saponin monomer 13 of the Dwarf lilyturf tuber, inhibited tumor metastasis and angiogenesis in previous studies. However, there is scarcity of data regarding the effect of DT-13 on autophagy process. Here, we demonstrated that DT-13 induced autophagy in human cancer cell lines and caused significant cell apoptosis under nutrient starvation. We firstly showed that DT-13 increased the accumulation of GFP-LC3 puncta and induced the expression of LC3-II in a dose- and time-dependent manner. DT-13 also upregulated the expression of Beclin-1, Atg-3 and Atg-7, and induced autophagic flux in human gastric cancer BGC-823 cells. We next found that low-toxic concentrations of DT-13 significantly induced apoptosis under nutrient deprivation. We finally demonstrated that the PI3K/Akt/mTOR signal pathway was involved in the cytotoxic effect of DT-13. Our data indicated that DT-13 was a novel autophagy inducer and might be considered in future treatment of cancer. PMID:27079642

  10. Chronic sleep deprivation and seasonality: implications for the obesity epidemic.

    PubMed

    Cizza, G; Requena, M; Galli, G; de Jonge, L

    2011-11-01

    Sleep duration has progressively fallen over the last 100 years while obesity has increased in the past 30 years. Several studies have reported an association between chronic sleep deprivation and long-term weight gain. Increased energy intake due to sleep loss has been listed as the main mechanism. The consequences of chronic sleep deprivation on energy expenditure have not been fully explored. Sleep, body weight, mood and behavior are subjected to circannual changes. However, in our modern environment seasonal changes in light and ambient temperature are attenuated. Seasonality, defined as cyclic changes in mood and behavior, is a stable personality trait with a strong genetic component. We hypothesize that the attenuation in seasonal changes in the environment may produce negative consequences, especially in individuals more predisposed to seasonality, such as women. Seasonal affective disorder, a condition more common in women and characterized by depressed mood, hypersomnia, weight gain, and carbohydrate craving during the winter, represents an extreme example of seasonality. One of the postulated functions of sleep is energy preservation. Hibernation, a phenomenon characterized by decreased energy expenditure and changes in the state of arousal, may offer useful insight into the mechanisms behind energy preservation during sleep. The goals of this article are to: a) consider the contribution of changes in energy expenditure to the weight gain due to sleep loss; b) review the phenomena of seasonality, hibernation, and their neuroendocrine mechanisms as they relate to sleep, energy expenditure, and body weight regulation. PMID:21720205

  11. Sleep deprivation attenuates experimental stroke severity in rats.

    PubMed

    Moldovan, Mihai; Constantinescu, Alexandra Oana; Balseanu, Adrian; Oprescu, Nicoleta; Zagrean, Leon; Popa-Wagner, Aurel

    2010-03-01

    Indirect epidemiological and experimental evidence suggest that the severity of injury during stroke is influenced by prior sleep history. The aim of our study was to test the effect of acute sleep deprivation on early outcome following experimental stroke. Young male Sprague-Dawley rats (n=20) were subjected to focal cerebral ischemia by reversible right middle cerebral artery occlusion (MCAO) for 90 min. In 10 rats, MCAO was performed just after 6-h of total sleep deprivation (TSD) by "gentle handling", whereas the other rats served as controls. Neurological function during the first week after stroke was monitored using a battery of behavioral tests investigating the asymmetry of sensorimotor deficit (tape removal test and cylinder test), bilateral sensorimotor coordination (rotor-rod and Inclined plane) and memory (T-maze and radial maze). Following MCAO, control rats had impaired behavioral performance in all tests. The largest impairment was noted in the tape test where the tape removal time from the left forelimb (contralateral to MCAO) was increased by approximately 10 fold (p<0.01). In contrast, rats subjected to TSD had complete recovery of sensorimotor performance consistent with a 2.5 fold smaller infarct volume and reduced morphological signs of neuronal injury at day 7 after MCAO. Our data suggest that brief TSD induces a neuroprotective response that limits the severity of a subsequent stroke, similar to rapid ischemic preconditioning. PMID:20045410

  12. Iron in intracellular infection: to provide or to deprive?

    PubMed Central

    Silva-Gomes, Sandro; Vale-Costa, Sílvia; Appelberg, Rui; Gomes, Maria S.

    2013-01-01

    Due to their chemical versatility, transition metals were incorporated as cofactors for several basic metabolic pathways in living organisms. This same characteristic makes them potentially harmful, since they can be engaged in deleterious reactions like Fenton chemistry. As such, organisms have evolved highly specialized mechanisms to supply their own metal needs while keeping their toxic potential in check. This dual character comes into play in host-pathogen interactions, given that the host can either deprive the pathogen of these key nutrients or exploit them to induce toxicity toward the invading agent. Iron stands as the prototypic example of how a metal can be used to limit the growth of pathogens by nutrient deprivation, a mechanism widely studied in Mycobacterium infections. However, the host can also take advantage of iron-induced toxicity to control pathogen proliferation, as observed in infections caused by Leishmania. Whether we may harness either of the two pathways for therapeutical purposes is still ill-defined. In this review, we discuss how modulation of the host iron availability impacts the course of infections, focusing on those caused by two relevant intracellular pathogens, Mycobacterium and Leishmania. PMID:24367768

  13. Neuroendocrine dysregulation following early social deprivation in children.

    PubMed

    Fries, Alison B Wismer; Shirtcliff, Elizabeth A; Pollak, Seth D

    2008-09-01

    Human and nonhuman animal studies reveal that early experiences with caregivers shape children's ability to regulate their responses to stress. To understand the effects of early deprivation on the regulation of the hypothalamic-pituitary-adrenal axis following social interactions, we examined urinary cortisol levels in a group of internationally adopted children who had experienced institutional care, and thus, species-atypical attachment relationships, early in life prior to adoption. Cortisol regulation was assessed both basally and following standardized interpersonal interactions between the child and his/her mother and the child and an unfamiliar adult. Postinstitutionalized children showed prolonged elevations in cortisol levels following the mother, but not the stranger, interaction. More severe neglect was associated with the highest basal cortisol levels and the most impaired cortisol regulation following the mother interaction. These results suggest that early social deprivation may contribute to long-term regulatory problems of the stress-responsive system, and that these differences are most evident within the context of ongoing, close interpersonal relationships. PMID:18683181

  14. Motor Outcomes in Children Exposed to Early Psychosocial Deprivation

    PubMed Central

    Levin, April R.; Zeanah, Charles H.; Fox, Nathan A.; Nelson, Charles A.

    2013-01-01

    Objectives To determine the effect of psychosocial deprivation early in life on motor development and assess the impact of a foster care intervention on improving motor development. Study design In a randomized controlled trial, children living in Romanian institutions were randomly assigned to care as usual in the institution, or placed in family centered foster care as part of the Bucharest Early Intervention Project (BEIP). The average age of placement into foster care was 23 months. At 8 years of age, the Bruininks-Oseretsky 2nd edition, short form (BOT2-SF) assessed the motor proficiency of children in both groups, as well as a never-institutionalized group from the Romanian community. Results Children in the never-institutionalized group did significantly better on the BOT2-SF than children who had ever been institutionalized. (p < .001). There was no significant difference in performance between children in the care as usual group and foster care group. This finding also held true for all individual items on the BOT2-SF, except sit-ups. Regression analyses revealed that the between-group and within-group differences in BOT2-SF scores were largely mediated by IQ. Conclusions Early deprivation had a negative effect on motor development which was not resolved by placement in foster care. This effect was predominantly mediated by IQ. This study highlights the importance of monitoring for and addressing motor delays in children with a history of institutionalization, particularly those children with low IQ. PMID:24161221

  15. Altered salience network connectivity predicts macronutrient intake after sleep deprivation

    PubMed Central

    Fang, Zhuo; Spaeth, Andrea M.; Ma, Ning; Zhu, Senhua; Hu, Siyuan; Goel, Namni; Detre, John A.; Dinges, David F.; Rao, Hengyi

    2015-01-01

    Although insufficient sleep is a well-recognized risk factor for overeating and weight gain, the neural mechanisms underlying increased caloric (particularly fat) intake after sleep deprivation remain unclear. Here we used resting-state functional magnetic resonance imaging and examined brain connectivity changes associated with macronutrient intake after one night of total sleep deprivation (TSD). Compared to the day following baseline sleep, healthy adults consumed a greater percentage of calories from fat and a lower percentage of calories from carbohydrates during the day following TSD. Subjects also exhibited increased brain connectivity in the salience network from the dorsal anterior cingulate cortex (dACC) to bilateral putamen and bilateral anterior insula (aINS) after TSD. Moreover, dACC-putamen and dACC-aINS connectivity correlated with increased fat and decreased carbohydrate intake during the day following TSD, but not during the day following baseline sleep. These findings provide a potential neural mechanism by which sleep loss leads to increased fat intake. PMID:25645575

  16. Noise and social deprivation in an urban environment

    NASA Astrophysics Data System (ADS)

    Shield, Bridget; Dockrell, Julie

    2001-05-01

    Noise levels have been measured inside and outside approximately 170 schools in London, England, as part of a project to investigate the effects of noise on the cognitive performance and academic attainments of children of primary school age in London. As well as providing data on individual schools the survey has provided a portrait of the noise climate across London. In addition to noise levels, the external noise sources present at each measurement location have been identified. The locations in which external schools noise levels were measured include areas where road traffic is the predominant noise source and areas near Heathrow Airport where aircraft are the major source. In addition to noise data, the following socioeconomic information has been obtained for a majority of the schools: percentages of children at each school having free school meals and the numbers for whom English is not the first language. The first of these is known to be a reliable indicator of social deprivation in an area. The relationship between noise and these socioeconomic factors has been established, which shows that, as might be expected, the higher noise levels in London are associated with the areas of greater social deprivation.

  17. Oxidative metabolism, ROS and NO under oxygen deprivation.

    PubMed

    Blokhina, Olga; Fagerstedt, Kurt V

    2010-05-01

    Oxygen deprivation, in line with other stress conditions, is accompanied by reactive oxygen (ROS) and nitrogen species (RNS) formation and is characterised by a set of metabolic changes collectively named as the 'oxidative stress response'. The controversial induction of oxidative metabolism under the lack of oxygen is necessitated by ROS and RNS signaling in the induction of adaptive responses, and inevitably results in oxidative damage. To prevent detrimental effects of oxidative stress, the levels of ROS and NO are tightly controlled on transcriptional, translational and metabolic levels. Hypoxia triggers the induction of genes responsible for ROS and NO handling and utilization (respiratory burst oxidase, non-symbiotic hemoglobins, several cytochromes P450, mitochondrial dehydrogenases, and antioxidant-related transcripts). The level of oxygen in the tissue is also under metabolic control via multiple mechanisms: Regulation of glycolytic and fermentation pathways to manage pyruvate availability for respiration, and adjustment of mitochondrial electron flow through NO and ROS balance. Both adaptive strategies are controlled by energy status and aim to decrease the respiratory capacity and to postpone complete anoxia. Besides local oxygen concentration, ROS and RNS formation is controlled by an array of antioxidants. Hypoxic treatment leads to the upregulation of multiple transcripts associated with ascorbate, glutathione and thioredoxin metabolism. The production of ROS and NO is an integral part of the response to oxygen deprivation which encompasses several levels of metabolic regulation to sustain redox signaling and to prevent oxidative damage. PMID:20303775

  18. Changes in direct current potentials during sleep deprivation.

    PubMed

    Hoffmann, R F; Bonato, R A; Armitage, R; Wimmer, F L

    1996-09-01

    Previous research reported changes in steady-state brain electrical activity during sleep. However, due to the quasi-linear nature of the Direct Current (DC) changes, artifact contamination was a potential confound. The present study was performed to further explore DC potentials and to help establish its validity. Twenty-five male university students (13 control and 12 sleep-deprived; mean age 19 y (range 17-27 y) served as subjects. During wakefulness, subjects were tested every hour while standard EEG activity recordings were made, as well as DC measurement. Split plot analyses of variance (ANOVAs) revealed that changes in DC activity levels differed between the two groups. The control subjects showed the same pattern of decreasing DC observed previously with a return to baseline levels during waking hours. The sleep-deprived subjects showed a smaller decrease in DC level through the night, followed by a rise in DC level that continued until the end of the 24 h study. It was concluded that DC measurement reflects changes in brain state associated with fatigue that are not attributable to artifactual processes. PMID:8956203

  19. Effects of food deprivation on the larvae of two flatfishes

    USGS Publications Warehouse

    Gadomski, D.M.; Petersen, J.H.

    1988-01-01

    For greatest survival, first-feeding halibut Paralichthys californicus and diamond turbot Hypsopsetta guttulata required food by the day of total yolk absorption. Some halibut larvae survived if fed 1 or 2 d after yolk depletion, but their growth rate was significantly less than larvae fed earlier. Survival of 3-wk-old larvae was greater in treatments with shorter starvation periods. A small percentage of 3-wk-old halibut larvae recovered from a maximum starvation period of 4 d while 3-wk-old diamond turbot successfully resumed feeding any time during food deprivation intervals lasting up to 9 d. Longer periods of starvation resulted in significant morphological differences – diamond turbot starved longer were not only smaller, but also less developed. In the field, larvae may experience varying periods of food deprivation due to differing spatial and temporal prey patch distributions. Our results demonstrate that differences in starvation resistance, and possibly mortality under patchy feeding conditions, are ontogenetic and species-specific.

  20. Glutamine deprivation initiates reversible assembly of mammalian rods and rings.

    PubMed

    Calise, S John; Carcamo, Wendy C; Krueger, Claire; Yin, Joyce D; Purich, Daniel L; Chan, Edward K L

    2014-08-01

    Rods and rings (RR) are protein assemblies composed of cytidine triphosphate synthetase type 1 (CTPS1) and inosine monophosphate dehydrogenase type 2 (IMPDH2), key enzymes in CTP and GTP biosynthesis. Small-molecule inhibitors of CTPS1 or IMPDH2 induce RR assembly in various cancer cell lines within 15 min to hours. Since glutamine is an essential amide nitrogen donor in these nucleotide biosynthetic pathways, glutamine deprivation was examined to determine whether it leads to RR formation. HeLa cells cultured in normal conditions did not show RR, but after culturing in media lacking glutamine, short rods (<2 μm) assembled after 24 h, and longer rods (>5 μm) formed after 48 h. Upon supplementation with glutamine or guanosine, these RR underwent almost complete disassembly within 15 min. Inhibition of glutamine synthetase with methionine sulfoximine also increased RR assembly in cells deprived of glutamine. Taken together, our data support the hypothesis that CTP/GTP biosynthetic enzymes polymerize to form RR in response to a decreased intracellular level of glutamine. We speculate that rod and ring formation is an adaptive metabolic response linked to disruption of glutamine homeostasis. PMID:24477477

  1. Deprivation, immigration and tuberculosis incidence in Naples, 1996-2000.

    PubMed

    Ponticiello, Antonio; Sturkenboom, Miriam C J M; Simonetti, Andrea; Ortolani, Rosanna; Malerba, Mario; Sanduzzi, Alessandro

    2005-01-01

    Most of the tuberculosis cases in Campania occur in Naples, the biggest city in the South of Italy with the highest unemployment and immigration rates. However, the occurrence of tuberculosis differs between the different neighbourhoods and it is not known whether these differences are associated with poverty or with immigration. We describe tuberculosis incidence and its association with socio-economic status and immigration in the city of Naples during the period 1996-2000. The basic design was an ecological study, correlating the incidence of tuberculosis which was calculated on the basis of notified tuberculosis cases to census data on immigration and socio-economic deprivation per neighbourhood. Immigrants had a high risk for tuberculosis (RR=34 for Africans) but the incidence of TB varied largely by districts and seemed independent of immigration. All socioeconomic factors increased the incidence of TB significantly. In a multivariate Poisson regression analysis only the rate of unemployment (p=0.02) and the population density (p=0.002) remained independently associated with tuberculosis incidence. In this study we showed that deprivation explained differences in tuberculosis incidence in Naples to a greater extent than immigration. PMID:16151887

  2. A polymorphism at the translation start site of the vitamin D receptor gene is associated with the response to anti-osteoporotic therapy in postmenopausal women from southern Italy.

    PubMed

    Conti, Valeria; Russomanno, Giusy; Corbi, Graziamaria; Toro, Giuseppe; Simeon, Vittorio; Filippelli, Walter; Ferrara, Nicola; Grimaldi, Michela; D'Argenio, Valeria; Maffulli, Nicola; Filippelli, Amelia

    2015-01-01

    The present study investigated the effect of two single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene, rs1544410 A/G and rs2228570 C/T, in modulating bone mineral density (BMD) and the response to treatment with bisphosphonates or strontium ranelate in postmenopausal osteoporosis (PMO). Four hundred eighteen postmenopausal women from Southern Italy treated with bisphosphonates or strontium ranelate for three years were enrolled and stratified according to their genotype. Changes in BMD were expressed as the delta t-scoret-score). Allelic frequencies for rs1544410 A/GSNP were 11.2% AA, 50.0% GA and 38.8% GG; for rs2228570 C/TSNP were 54.8% CC, 39.5% TC and 5.7% TT. TT carriers showed a lower t-score than TC and CC (both p < 0.02) genotypes and were more responsive to the therapy when compared to both TC (p < 0.02) and CC (p < 0.05) carriers. Specifically, TT carriers receiving alendronate demonstrated a significant improvement of the Δt-score compared to TC and CC (both p < 0.0001) carriers. After adjustment for confounders, the Δt-score showed evidence of a statistically significant positive association with TT in all treatments considered. Therapy response was independent of rs1544410 A/G SNP; instead, rs2228570 C/TSNP was associated with a better response to antiresorptive treatment, thus suggesting that the therapy for PMO should be personalized. PMID:25764158

  3. A Polymorphism at the Translation Start Site of the Vitamin D Receptor Gene Is Associated with the Response to Anti-Osteoporotic Therapy in Postmenopausal Women from Southern Italy

    PubMed Central

    Conti, Valeria; Russomanno, Giusy; Corbi, Graziamaria; Toro, Giuseppe; Simeon, Vittorio; Filippelli, Walter; Ferrara, Nicola; Grimaldi, Michela; D’Argenio, Valeria; Maffulli, Nicola; Filippelli, Amelia

    2015-01-01

    The present study investigated the effect of two single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene, rs1544410 A/G and rs2228570 C/T, in modulating bone mineral density (BMD) and the response to treatment with bisphosphonates or strontium ranelate in postmenopausal osteoporosis (PMO). Four hundred eighteen postmenopausal women from Southern Italy treated with bisphosphonates or strontium ranelate for three years were enrolled and stratified according to their genotype. Changes in BMD were expressed as the delta t-scoret-score). Allelic frequencies for rs1544410 A/GSNP were 11.2% AA, 50.0% GA and 38.8% GG; for rs2228570 C/TSNP were 54.8% CC, 39.5% TC and 5.7% TT. TT carriers showed a lower t-score than TC and CC (both p < 0.02) genotypes and were more responsive to the therapy when compared to both TC (p < 0.02) and CC (p < 0.05) carriers. Specifically, TT carriers receiving alendronate demonstrated a significant improvement of the Δt-score compared to TC and CC (both p < 0.0001) carriers. After adjustment for confounders, the Δt-score showed evidence of a statistically significant positive association with TT in all treatments considered. Therapy response was independent of rs1544410 A/G SNP; instead, rs2228570 C/TSNP was associated with a better response to antiresorptive treatment, thus suggesting that the therapy for PMO should be personalized. PMID:25764158

  4. The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation.

    PubMed

    McQuarrie, Emily P; Mackinnon, Bruce; McNeice, Valerie; Fox, Jonathan G; Geddes, Colin C

    2014-01-01

    Chronic kidney disease is more common in areas of socioeconomic deprivation, but the relationship with the incidence and diagnosis of biopsy-proven renal disease is unknown. In order to study this, all consecutive adult patients undergoing renal biopsy in West and Central Scotland over an 11-year period were prospectively analyzed for demographics, indication, and histologic diagnosis. Using the Scottish Index of Multiple Deprivation, 1555 eligible patients were separated into quintiles of socioeconomic deprivation according to postcode. Patients in the most deprived quintile were significantly more likely to undergo biopsy compared with patients from less deprived areas (109.5 compared to 95.9 per million population/year). Biopsy indications were significantly more likely to be nephrotic syndrome, or significant proteinuria without renal impairment. Patients in the most deprived quintile were significantly more likely to have glomerulonephritis. There was a significant twofold increase in the diagnosis of IgA nephropathy in the patients residing in the most compared with the least deprived postcodes not explained by the demographics of the underlying population. Thus, patients from areas of socioeconomic deprivation in West and Central Scotland are significantly more likely to undergo native renal biopsy and have a higher prevalence of IgA nephropathy. PMID:24025641

  5. Replication and Pedagogy in the History of Psychology IV: Patrick and Gilbert (1896) on Sleep Deprivation

    ERIC Educational Resources Information Center

    Fuchs, Thomas; Burgdorf, Jeffrey

    2008-01-01

    We report an attempted replication of G. T. W. Patrick and J. A. Gilbert's pioneering sleep deprivation experiment "Studies from the psychological laboratory of the University of Iowa. On the effects of loss of sleep", conducted in 1895/96. Patrick and Gilbert's study was the first sleep deprivation experiment of its kind, performed by some of the…

  6. Survival and Success at Secondary School Stage: Looking beyond the Explanation of Socio-Cultural Deprivation

    ERIC Educational Resources Information Center

    Sarangi, Dibakar; Panda, Smita Rani

    2013-01-01

    A wide spectrum of research literature pointed out socio-cultural deprivation as the dominant explanation for student survival and success in schools. This paper, contending socio-cultural deprivation as inadequate explanation for dropout and detention at secondary level, probed into the role of pupils' foundation knowledge in their survival…

  7. Suicide by Oxygen Deprivation with Helium: A Preliminary Study of British Columbia Coroner Investigations

    ERIC Educational Resources Information Center

    Ogden, Russel D.; Hassan, Shereen

    2011-01-01

    This article researches a relatively new suicide method advanced by right-to-die organizations: oxygen deprivation by breathing helium inside a plastic hood. The article begins with a review of the role of the coroner and the history of oxygen deprivation with helium; it then examines 20 Judgements of Inquiry (JOI) by British Columbia coroners…

  8. Using Non-Monetary Deprivation Indicators to Analyze Poverty and Social Exclusion: Lessons from Europe?

    ERIC Educational Resources Information Center

    Nolan, Brian; Whelan, Christopher T.

    2010-01-01

    Non-monetary indicators of deprivation are now widely used in studying poverty in Europe. While measuring financial resources remains central, having reliable information about material deprivation adds to the ability to capture poverty and social exclusion. Non-monetary indicators can help improve the identification of those experiencing poverty…

  9. EFFECTIVENESS OF THE HEAD START PROGRAM IN ENHANCING SCHOOL READINESS OF CULTURALLY DEPRIVED CHILDREN.

    ERIC Educational Resources Information Center

    CHESTEEN, HILLIARD E., JR.; AND OTHERS

    TO STUDY THE EFFECT OF A 6-WEEK HEAD START PROGRAM ON THE SCHOOL READINESS OF 81 CULTURALLY DEPRIVED CHILDREN IN EAST BATON ROUGE PARISH, LOUISIANA, COMPARISONS WERE MADE BETWEEN HEAD START AND NONCULTURALLY DEPRIVED CHILDREN. IQ SCORES AND CULTURAL-SOCIOLOGICAL-ECONOMICAL STATUS INFLUENCE UPON SCHOOL READINESS WERE STUDIED. ALL CHILDREN INVOLVED…

  10. Social Competence of Adult Chimpanzees ("Pan troglodytes") with Severe Deprivation History: I. An Individual Approach

    ERIC Educational Resources Information Center

    Kalcher-Sommersguter, Elfriede; Preuschoft, Signe; Crailsheim, Karl; Franz, Cornelia

    2011-01-01

    Early social deprivation in highly social mammals interferes with their varying needs for security and stimulation. Toleration of social stimulation was studied in 18 adult ex-laboratory chimpanzees, who had been deprived for 16 to 27 years, during their 1st year after resocialization into 1 of 3 social groups. For this, a model of social…

  11. Sleepless in Adolescence: Prospective Data on Sleep Deprivation, Health and Functioning

    ERIC Educational Resources Information Center

    Roberts, Robert E.; Roberts, Catherine Ramsay; Duong, Hao T.

    2009-01-01

    We estimate prevalence, incidence and persistence of short sleep or sleep deprivation in a two wave cohort study of 4175 youths 11-17 years old at baseline and 3134 of these a year later. Data were collected using computer interviews and questionnaires. Sleep deprivation was defined as 6 h or less per night during the past 4 weeks. Weighted…

  12. Physical Growth and Maturation Following Early Severe Institutional Deprivation: Do They Mediate Specific Psychopathological Effects?

    ERIC Educational Resources Information Center

    Sonuga-Barke, Edmund J.; Schlotz, Wolff; Rutter, Michael

    2010-01-01

    The authors' previous work and the data reported in the preceding chapters of this monograph provide conclusive evidence of the persistent nature of the negative impact of early severe deprivation. Institutional deprivation, despite the good outcomes for many, was often associated with substantial impairment and disorder across a wide range of…

  13. Recognition of Pictorial Material As A Function of Experiential Deprivation and Age.

    ERIC Educational Resources Information Center

    Misra, Girishwar; Shukla, Aradhana

    1984-01-01

    Investigated relative effects of chronological age and experiential deprivation upon pictorial recognition. Four age levels (ages four to five, five to six, six to seven, and seven to eight years) and two levels of deprivation were manipulated. The 50 subjects in each factorial cell performed tasks individually. (Author/RH)

  14. What Factors Are Important in Smoking Cessation Amongst Deprived Communities?: A Qualitative Study

    ERIC Educational Resources Information Center

    Henderson, Hazel J.; Memon, Anjum; Lawson, Kate; Jacobs, Barbara; Koutsogeorgou, Eleni

    2011-01-01

    Objective: There is limited evidence regarding effective smoking cessation interventions in deprived communities. This study explored what factors are considered most important in smoking cessation, from the perspective of a group of NHS Stop Smoking Service users from a deprived community. Design: A qualitative study. Setting: A deprived…

  15. Effects of one night of sleep deprivation on hormone profiles and performance efficiency.

    PubMed

    Goh, V H; Tong, T Y; Lim, C L; Low, E C; Lee, L K

    2001-05-01

    This study examined the effects of one night of sleep deprivation on melatonin and cortisol profiles, as well as performance efficiency of military service members. Sleep intervention consisted of total lack of sleep (N = 7) or 8 hours of sleep (control group; N = 7) during the night. All parameters were measured at selected time intervals before (day 1), during (only in sleep-deprived individuals), and after (day 2) sleep intervention. Rotary pursuit scores and handgrip strength data were used as indices of psychomotor and physical performance, respectively. In sleep-deprived individuals, more salivary melatonin, but not cortisol, was secreted than in subjects who slept adequately. Significant increases in melatonin and cortisol were noted, especially at 1:30 p.m. on the day after nighttime sleep deprivation. In contrast, the tracking scores for rotary pursuit and grip strength among sleep-deprived and rested individuals were comparable. Across a normal working day (day 1), all parameters studied revealed time-specific fluctuations in both control and sleep-deprived groups. Irrespective of nighttime sleep schedule, the patterns of performance on day 2 differed from those on day 1. The tracking performance improved on day 2, whereas grip strength worsened, which may reflect inherent learning and muscle fatigue, respectively. During the night of sleep deprivation, performance declined. In conclusion, the present study showed that one night of sleep deprivation (8 hours) resulted in significant hormonal changes on the next afternoon but did not modify tracking and muscular strength performance. PMID:11370208

  16. Short-term visual deprivation can enhance spatial release from masking.

    PubMed

    Pagé, Sara; Sharp, Andréanne; Landry, Simon P; Champoux, François

    2016-08-15

    This research aims to study the effect of short-term visual deprivation on spatial release from masking, a major component of the cocktail party effect that allows people to detect an auditory target in noise. The Masking Level Difference (MLD) test was administered on healthy individuals over three sessions: before (I) and after 90min of visual deprivation (II), and after 90min of re-exposure to light (III). A non-deprived control group performed the same tests, but remained sighted between sessions I and II. The non-deprived control group displayed constant results across sessions. However, performance in the MLD test was improved following short-term visual deprivation and performance returned to pre-deprivation values after light re-exposure. This study finds that short-term visual deprivation transiently enhances the spatial release from masking. These data suggest the significant potential for enhancing a process involved in the cocktail party effect in normally developing individuals and adds to an emerging literature on the potential to enhance auditory ability after only a brief period of visual deprivation. PMID:27329242

  17. Adult Visual Experience Promotes Recovery of Primary Visual Cortex from Long-Term Monocular Deprivation

    ERIC Educational Resources Information Center

    Fischer, Quentin S.; Aleem, Salman; Zhou, Hongyi; Pham, Tony A.

    2007-01-01

    Prolonged visual deprivation from early childhood to maturity is believed to cause permanent visual impairment. However, there have been case reports of substantial improvement of binocular vision in human adults following lifelong visual impairment or deprivation. These observations, together with recent findings of adult ocular dominance…

  18. Income Inequality Indices Interpreted as Measures of Relative Deprivation/Satisfaction

    ERIC Educational Resources Information Center

    Imedio-Olmedo, Luis Jose; Parrado-Gallardo, Encarnacion M.; Barcena-Martin, Elena

    2012-01-01

    This paper considers different ways of making comparisons between individuals in terms of deprivation and/or satisfaction. This allows the Gini index, the Bonferroni index and the De Vergottini index to be interpreted as social deprivation measures as well as social satisfaction measures. The inequality measures that belong to the [beta] family,…

  19. New Comparative Measures of Income, Material Deprivation, and Well-Being

    ERIC Educational Resources Information Center

    Smeeding, Timothy M.

    2009-01-01

    Most societies, rich and poor, seek to measure progress in reducing poverty and need, as indicated by material deprivation or social exclusion. The yardsticks used to assess progress and policy impact mainly include income-based poverty, but broader measures of poverty based on consumption, wealth, and material deprivation are also now coming into…

  20. Beyond Stimulus Deprivation: Iron Deficiency and Cognitive Deficits in Postinstitutionalized Children

    ERIC Educational Resources Information Center

    Doom, Jenalee R.; Gunnar, Megan R.; Georgieff, Michael K.; Kroupina, Maria G.; Frenn, Kristin; Fuglestad, Anita J.; Carlson, Stephanie M.

    2014-01-01

    Children adopted from institutions have been studied as models of the impact of stimulus deprivation on cognitive development (Nelson, Bos, Gunnar, & Sonuga-Barke, 2011), but these children may also suffer from micronutrient deficiencies (Fuglestad et al., 2008). The contributions of iron deficiency (ID) and duration of deprivation on…

  1. Short-Term Visual Deprivation, Tactile Acuity, and Haptic Solid Shape Discrimination

    PubMed Central

    Crabtree, Charles E.; Norman, J. Farley

    2014-01-01

    Previous psychophysical studies have reported conflicting results concerning the effects of short-term visual deprivation upon tactile acuity. Some studies have found that 45 to 90 minutes of total light deprivation produce significant improvements in participants' tactile acuity as measured with a grating orientation discrimination task. In contrast, a single 2011 study found no such improvement while attempting to replicate these earlier findings. A primary goal of the current experiment was to resolve this discrepancy in the literature by evaluating the effects of a 90-minute period of total light deprivation upon tactile grating orientation discrimination. We also evaluated the potential effect of short-term deprivation upon haptic 3-D shape discrimination using a set of naturally-shaped solid objects. According to previous research, short-term deprivation enhances performance in a tactile 2-D shape discrimination task – perhaps a similar improvement also occurs for haptic 3-D shape discrimination. The results of the current investigation demonstrate that not only does short-term visual deprivation not enhance tactile acuity, it additionally has no effect upon haptic 3-D shape discrimination. While visual deprivation had no effect in our study, there was a significant effect of experience and learning for the grating orientation task – the participants' tactile acuity improved over time, independent of whether they had, or had not, experienced visual deprivation. PMID:25397327

  2. [Variations of time perspective by social deprivation, what are the effects on smoking cessation?].

    PubMed

    Merson, F; Guillon, C; Arvers, P; Underner, M; Perriot, J

    2012-10-01

    Smoking represents a major public health problem because of its high morbidity and mortality rates. Nearly half of the deaths in the lower class are caused by smoking. The socially deprived are physically and psychologically vulnerable. The instability of their situation increases the difficulty to invest in smoking cessation and certain time orientations linked to this social deprivation represent negative factors in the prognosis. Socially deprived populations do not understand the consequences of smoking unless they are in denial of the risks. The motivation to stop is essentially financial. The perception of smoking cessation is taken as a deprivation of pleasure. Independently of the social deprivation factors, taking into account the time perspective conveys necessary information of appropriate care. PMID:23167164

  3. The Effects of 24-hour Sleep Deprivation on the Exploration-Exploitation Trade-off

    PubMed Central

    Glass, Brian D.; Maddox, W. Todd; Bowen, Christopher; Savarie, Zachary R.; Matthews, Michael D.; Markman, Arthur B.; Schnyer, David M.

    2010-01-01

    Sleep deprivation has a complex set of neurological effects that go beyond a mere slowing of mental processes. While cognitive and perceptual impairments in sleep deprived individuals are widespread, some abilities remain intact. In an effort to characterize these effects, some have suggested an impairment of complex decision making ability despite intact ability to follow simple rules. To examine this trade-off, 24-hour total sleep deprived individuals performed two versions of a resource acquisition foraging task, one in which exploration is optimal (to succeed, abandon low value, high saliency options) and another in which exploitation is optimal (to succeed, refrain from switching between options). Sleep deprived subjects exhibited decreased performance on the exploitation task compared to non-sleep deprived controls, yet both groups exhibited increased performance on the exploratory task. These results speak to previous neuropsychological work on cognitive control. PMID:21686036

  4. Sleep deprivation influences some but not all processes of supervisory attention

    NASA Technical Reports Server (NTRS)

    Jennings, J. R.; Monk, T. H.; van der Molen, M. W.

    2003-01-01

    Does one night of sleep deprivation alter processes of supervisory attention in general or only a specific subset of such processes? Twenty college-aged volunteers, half female, performed a choice reaction time task. A cue indicated that compatible (e.g., right button, right-pointing arrow) or incompatible (e.g., left button, right-pointing arrow) responses were to be given to a stimulus that followed 50 or 500 ms later. The paradigm assessed response inhibition, task-shifting skill, and task strategy-processes inherent in supervisory attention. Performance, along with heart rate, was assessed for 12 hr following normal sleep or a night of complete sleep deprivation. Sleep deprivation altered neither preparation for task shifting nor response inhibition. The ability to use preparatory bias to speed performance did decrease with sleep deprivation. Sleep deprivation appears to selectively affect this supervisory attention process, which is perceived as an active effort to cope with a challenging task.

  5. c-MYC responds to glucose deprivation in a cell-type-dependent manner.

    PubMed

    Wu, S; Yin, X; Fang, X; Zheng, J; Li, L; Liu, X; Chu, L

    2015-01-01

    Metabolic reprogramming supports cancer cells' demands for rapid proliferation and growth. Previous work shows that oncogenes, such as MYC, hypoxia-inducible factor 1 (HIF1), have a central role in driving metabolic reprogramming. A lot of metabolic enzymes, which are deregulated in most cancer cells, are the targets of these oncogenes. However, whether metabolic change affects these oncogenes is still unclear. Here we show that glucose deprivation (GD) affects c-MYC protein levels in a cell-type-dependent manner regardless of P53 mutation status. GD dephosphorylates and then decreases c-MYC protein stability through PI3K signaling pathway in HeLa cells, but not in MDA-MB-231 cells. Role of c-MYC in sensitivity of GD also varies with cell types. c-MYC-mediated glutamine metabolism partially improves the sensitivity of GD in MDA-MB-231 cells. Our results reveal that the heterogeneity of cancer cells in response to metabolic stress should be considered in metabolic therapy for cancer. PMID:27551483

  6. c-MYC responds to glucose deprivation in a cell-type-dependent manner

    PubMed Central

    Wu, S; Yin, X; Fang, X; Zheng, J; Li, L; Liu, X; Chu, L

    2015-01-01

    Metabolic reprogramming supports cancer cells’ demands for rapid proliferation and growth. Previous work shows that oncogenes, such as MYC, hypoxia-inducible factor 1 (HIF1), have a central role in driving metabolic reprogramming. A lot of metabolic enzymes, which are deregulated in most cancer cells, are the targets of these oncogenes. However, whether metabolic change affects these oncogenes is still unclear. Here we show that glucose deprivation (GD) affects c-MYC protein levels in a cell-type-dependent manner regardless of P53 mutation status. GD dephosphorylates and then decreases c-MYC protein stability through PI3K signaling pathway in HeLa cells, but not in MDA-MB-231 cells. Role of c-MYC in sensitivity of GD also varies with cell types. c-MYC-mediated glutamine metabolism partially improves the sensitivity of GD in MDA-MB-231 cells. Our results reveal that the heterogeneity of cancer cells in response to metabolic stress should be considered in metabolic therapy for cancer. PMID:27551483

  7. Parkin Protects against Oxygen-Glucose Deprivation/Reperfusion Insult by Promoting Drp1 Degradation.

    PubMed

    Tang, Jiayu; Hu, Zhiping; Tan, Jieqiong; Yang, Sonlin; Zeng, Liuwang

    2016-01-01

    Ischemic stroke results in severe brain damage and remains one of the leading causes of death and disability worldwide. Effective neuroprotective therapies are needed to reduce brain damage resulting from ischemic stroke. Mitochondria are crucial for cellular energy production and homeostasis. Modulation of mitochondrial function mediates neuroprotection against ischemic brain damage. Dynamin-related protein 1 (Drp1) and parkin play a key role in regulating mitochondrial dynamics. They are potential therapeutic targets for neuroprotection in ischemic stroke. Protective effects of parkin-Drp1 pathway on mitochondria were assessed in a cellular ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces mitochondrial fragmentation. The expression of Drp1 protein is increased after OGDR insult, while the parkin protein level is decreased. The altered protein level of Drp1 after OGDR injury is mediated by parkin through ubiquitin proteasome system (UPS). Drp1 depletion protects against OGDR induced mitochondrial damage and apoptosis. Meanwhile, parkin overexpression protects against OGDR induced apoptosis and mitochondrial dysfunction, which is attenuated by increased expression of Drp1. Our data demonstrate that parkin protects against OGDR insult through promoting degradation of Drp1. This neuroprotective potential of parkin-Drp1 pathway against OGDR insult will pave the way for developing novel neuroprotective agents for cerebral ischemia-reperfusion related disorders. PMID:27597885

  8. Parkin Protects against Oxygen-Glucose Deprivation/Reperfusion Insult by Promoting Drp1 Degradation

    PubMed Central

    Tang, Jiayu; Hu, Zhiping; Tan, Jieqiong; Yang, Sonlin

    2016-01-01

    Ischemic stroke results in severe brain damage and remains one of the leading causes of death and disability worldwide. Effective neuroprotective therapies are needed to reduce brain damage resulting from ischemic stroke. Mitochondria are crucial for cellular energy production and homeostasis. Modulation of mitochondrial function mediates neuroprotection against ischemic brain damage. Dynamin-related protein 1 (Drp1) and parkin play a key role in regulating mitochondrial dynamics. They are potential therapeutic targets for neuroprotection in ischemic stroke. Protective effects of parkin-Drp1 pathway on mitochondria were assessed in a cellular ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces mitochondrial fragmentation. The expression of Drp1 protein is increased after OGDR insult, while the parkin protein level is decreased. The altered protein level of Drp1 after OGDR injury is mediated by parkin through ubiquitin proteasome system (UPS). Drp1 depletion protects against OGDR induced mitochondrial damage and apoptosis. Meanwhile, parkin overexpression protects against OGDR induced apoptosis and mitochondrial dysfunction, which is attenuated by increased expression of Drp1. Our data demonstrate that parkin protects against OGDR insult through promoting degradation of Drp1. This neuroprotective potential of parkin-Drp1 pathway against OGDR insult will pave the way for developing novel neuroprotective agents for cerebral ischemia-reperfusion related disorders. PMID:27597885

  9. Short-term monocular deprivation alters GABA in the adult human visual cortex.

    PubMed

    Lunghi, Claudia; Emir, Uzay E; Morrone, Maria Concetta; Bridge, Holly

    2015-06-01

    Neuroplasticity is a fundamental property of the nervous system that is maximal early in life, within the critical period [1-3]. Resting GABAergic inhibition is necessary to trigger ocular dominance plasticity and to modulate the onset and offset of the critical period [4, 5]. GABAergic inhibition also plays a crucial role in neuroplasticity of adult animals: the balance between excitation and inhibition in the primary visual cortex (V1), measured at rest, modulates the susceptibility of ocular dominance to deprivation [6-10]. In adult humans, short-term monocular deprivation strongly modifies ocular balance, unexpectedly boosting the deprived eye, reflecting homeostatic plasticity [11, 12]. There is no direct evidence, however, to support resting GABAergic inhibition in homeostatic plasticity induced by visual deprivation. Here, we tested the hypothesis that GABAergic inhibition, measured at rest, is reduced by deprivation, as demonstrated by animal studies. GABA concentration in V1 of adult humans was measured using ultra-high-field 7T magnetic resonance spectroscopy before and after short-term monocular deprivation. After monocular deprivation, resting GABA concentration decreased in V1 but was unaltered in a control parietal area. Importantly, across participants, the decrease in GABA strongly correlated with the deprived eye perceptual boost measured by binocular rivalry. Furthermore, after deprivation, GABA concentration measured during monocular stimulation correlated with the deprived eye dominance. We suggest that reduction in resting GABAergic inhibition triggers homeostatic plasticity in adult human V1 after a brief period of abnormal visual experience. These results are potentially useful for developing new therapeutic strategies that could exploit the intrinsic residual plasticity of the adult human visual cortex. PMID:26004760

  10. Identification of Genes Associated with Resilience/Vulnerability to Sleep Deprivation and Starvation in Drosophila

    PubMed Central

    Thimgan, Matthew S.; Seugnet, Laurent; Turk, John; Shaw, Paul J.

    2015-01-01

    Background and Study Objectives: Flies mutant for the canonical clock protein cycle (cyc01) exhibit a sleep rebound that is ∼10 times larger than wild-type flies and die after only 10 h of sleep deprivation. Surprisingly, when starved, cyc01 mutants can remain awake for 28 h without demonstrating negative outcomes. Thus, we hypothesized that identifying transcripts that are differentially regulated between waking induced by sleep deprivation and waking induced by starvation would identify genes that underlie the deleterious effects of sleep deprivation and/or protect flies from the negative consequences of waking. Design: We used partial complementary DNA microarrays to identify transcripts that are differentially expressed between cyc01 mutants that had been sleep deprived or starved for 7 h. We then used genetics to determine whether disrupting genes involved in lipid metabolism would exhibit alterations in their response to sleep deprivation. Setting: Laboratory. Patients or Participants: Drosophila melanogaster. Interventions: Sleep deprivation and starvation. Measurements and Results: We identified 84 genes with transcript levels that were differentially modulated by 7 h of sleep deprivation and starvation in cyc01 mutants and were confirmed in independent samples using quantitative polymerase chain reaction. Several of these genes were predicted to be lipid metabolism genes, including bubblegum, cueball, and CG4500, which based on our data we have renamed heimdall (hll). Using lipidomics we confirmed that knockdown of hll using RNA interference significantly decreased lipid stores. Importantly, genetically modifying bubblegum, cueball, or hll resulted in sleep rebound alterations following sleep deprivation compared to genetic background controls. Conclusions: We have identified a set of genes that may confer resilience/vulnerability to sleep deprivation and demonstrate that genes involved in lipid metabolism modulate sleep homeostasis. Citation: Thimgan MS

  11. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    SciTech Connect

    Volkow N. D.; Fowler J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi F.

    2012-03-23

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  12. Wheel-running reinforcement in free-feeding and food-deprived rats.

    PubMed

    Belke, Terry W; Pierce, W David

    2016-03-01

    Rats experiencing sessions of 30min free access to wheel running were assigned to ad-lib and food-deprived groups, and given additional sessions of free wheel activity. Subsequently, both ad-lib and deprived rats lever pressed for 60s of wheel running on fixed ratio (FR) 1, variable ratio (VR) 3, VR 5, and VR 10 schedules, and on a response-initiated variable interval (VI) 30s schedule. Finally, the ad-lib rats were switched to food deprivation and the food-deprived rats were switched to free food, as rats continued responding on the response-initiated VI 30-s schedule. Wheel running functioned as reinforcement for both ad-lib and food-deprived rats. Food-deprived rats, however, ran faster and had higher overall lever-pressing rates than free-feeding rats. On the VR schedules, wheel-running rates positively correlated with local and overall lever pressing rates for deprived, but not ad-lib rats. On the response-initiated VI 30s schedule, wheel-running rates and lever-pressing rates changed for ad-lib rats switched to food deprivation, but not for food-deprived rats switched to free-feeding. The overall pattern of results suggested different sources of control for wheel running: intrinsic motivation, contingencies of automatic reinforcement, and food-restricted wheel running. An implication is that generalizations about operant responding for wheel running in food-deprived rats may not extend to wheel running and operant responding of free-feeding animals. PMID:26631601

  13. Evidence for neuroprotective effect of sulbutiamine against oxygen-glucose deprivation in rat hippocampal CA1 pyramidal neurons.

    PubMed

    Kwag, Jeehyun; Majid, Aman Shah Abdul; Kang, Kui Dong

    2011-01-01

    Hippocampus is one of the earliest brain regions that gets affected by ischemia, however, no pharmacological therapy exists yet that can fully counteract the ischemic damage. Here we study the effect of sulbutiamine, a synthetic thiamine analogue that can cross the blood-brain barrier easily, on hippocampal neurons under an in vitro model of ischemia, oxygen-glucose deprivation (OGD). We find that exposure to OGD in the presence of sulbutiamine significantly increases neuronal viability and enhances electrophysiological properties such as excitatory synaptic transmissions and intrinsic neuronal membrane input resistance in a concentration-dependent manner. Overall, here we report, for the first time, the neuroprotective evidence of sulbutiamine on hippocampal CA1 pyramidal neurons under OGD, which may have beneficial implications as a possible therapeutic agent/substance against ischemic insult. PMID:22040892

  14. Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress.

    PubMed

    Pintana, Hiranya; Pongkan, Wanpitak; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2015-10-01

    Testosterone replacement improves metabolic parameters and cognitive function in hypogonadism. However, the effects of testosterone therapy on cognition in obese condition with testosterone deprivation have not been investigated. We hypothesized that testosterone replacement improves cognitive function in testosterone-deprived obese rats by restoring brain insulin sensitivity, brain mitochondrial function, and hippocampal synaptic plasticity. Thirty male Wistar rats had either a bilateral orchiectomy (ORX: O, n = 24) or a sham operation (S, n = 6). ORX rats were further divided into two groups fed with either a normal diet (NDO) or a high-fat diet (HFO) for 12 weeks. Then, ORX rats in each dietary group were divided into two subgroups (n = 6/subgroup) and were given either castor oil or testosterone (2 mg/kg/day, s.c.) for 4 weeks. At the end of this protocol, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity, and brain mitochondrial function were determined. We found that testosterone replacement increased peripheral insulin sensitivity, decreased circulation and brain oxidative stress levels, and attenuated brain mitochondrial ROS production in HFO rats. However, testosterone failed to restore hippocampal synaptic plasticity and cognitive function in HFO rats. In contrast, in NDO rats, testosterone decreased circulation and brain oxidative stress levels, attenuated brain mitochondrial ROS production, and restored hippocampal synaptic plasticity as well as cognitive function. These findings suggest that testosterone replacement improved peripheral insulin sensitivity and decreased oxidative stress levels, but failed to restore hippocampal synaptic plasticity and cognitive function in testosterone-deprived obese rats. However, it provided beneficial effects in reversing cognitive impairment in testosterone-deprived non-obese rats. PMID:26277724

  15. Exercise‐Induced growth hormone during acute sleep deprivation

    PubMed Central

    Ritsche, Kevin; Nindl, Bradly C.; Wideman, Laurie

    2014-01-01

    Abstract The effect of acute (24‐h) sleep deprivation on exercise‐induced growth hormone (GH) and insulin‐like growth factor‐1 (IGF‐1) was examined. Ten men (20.6 ± 1.4 years) completed two randomized 24‐h sessions including a brief, high‐intensity exercise bout following either a night of sleep (SLEEP) or (24‐h) sleep deprivation (SLD). Anaerobic performance (mean power [MP], peak power [PP], minimum power [MinP], time to peak power [TTPP], fatigue index, [FI]) and total work per sprint [TWPS]) was determined from four maximal 30‐sec Wingate sprints on a cycle ergometer. Self‐reported sleep 7 days prior to each session was similar between SLEEP and SLD sessions (7.92 ± 0.33 vs. 7.98 ± 0.39 h, P =0.656, respectively) and during the actual SLEEP session in the lab, the total amount of sleep was similar to the 7 days leading up to the lab session (7.72 ± 0.14 h vs. 7.92 ± 0.33 h, respectively) (P =0.166). No differences existed in MP, PP, MinP, TTPP, FI, TWPS, resting GH concentrations, time to reach exercise‐induced peak GH concentration (TTP), or free IGF‐1 between sessions. GH area under the curve (AUC) (825.0 ± 199.8 vs. 2212.9 ± 441.9 μg/L*min, P <0.01), exercise‐induced peak GH concentration (17.8 ± 3.7 vs. 39.6 ± 7.1 μg/L, P <0.01) and ΔGH (peak GH – resting GH) (17.2 ± 3.7 vs. 38.2 ± 7.3 μg/L, P <0.01) were significantly lower during the SLEEP versus SLD session. Our results indicate that the exercise‐induced GH response was significantly augmented in sleep‐deprived individuals. PMID:25281616

  16. Antioxidants, Oxidative Damage and Oxygen Deprivation Stress: a Review

    PubMed Central

    BLOKHINA, OLGA; VIROLAINEN, EIJA; FAGERSTEDT, KURT V.

    2003-01-01

    Oxidative stress is induced by a wide range of environmental factors including UV stress, pathogen invasion (hypersensitive reaction), herbicide action and oxygen shortage. Oxygen deprivation stress in plant cells is distinguished by three physiologically different states: transient hypoxia, anoxia and reoxygenation. Generation of reactive oxygen species (ROS) is characteristic for hypoxia and especially for reoxygenation. Of the ROS, hydrogen peroxide (H2O2) and superoxide (O2·–) are both produced in a number of cellular reactions, including the iron‐catalysed Fenton reaction, and by various enzymes such as lipoxygenases, peroxidases, NADPH oxidase and xanthine oxidase. The main cellular components susceptible to damage by free radicals are lipids (peroxidation of unsaturated fatty acids in membranes), proteins (denaturation), carbohydrates and nucleic acids. Consequences of hypoxia‐induced oxidative stress depend on tissue and/or species (i.e. their tolerance to anoxia), on membrane properties, on endogenous antioxidant content and on the ability to induce the response in the antioxidant system. Effective utilization of energy resources (starch, sugars) and the switch to anaerobic metabolism and the preservation of the redox status of the cell are vital for survival. The formation of ROS is prevented by an antioxidant system: low molecular mass antioxidants (ascorbic acid, glutathione, tocopherols), enzymes regenerating the reduced forms of antioxidants, and ROS‐interacting enzymes such as SOD, peroxidases and catalases. In plant tissues many phenolic compounds (in addition to tocopherols) are potential antioxidants: flavonoids, tannins and lignin precursors may work as ROS‐scavenging compounds. Antioxidants act as a cooperative network, employing a series of redox reactions. Interactions between ascorbic acid and glutathione, and ascorbic acid and phenolic compounds are well known. Under oxygen deprivation stress some contradictory results on the

  17. Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation.

    PubMed

    Wells, James W; Evans, Christopher H; Scott, Milcah C; Rütgen, Barbara C; O'Brien, Timothy D; Modiano, Jaime F; Cvetkovic, Goran; Tepic, Slobodan

    2013-01-01

    Rapidly growing tumor cells require a nutrient-rich environment in order to thrive, therefore, restricting access to certain key amino acids, such as arginine, often results in the death of malignant cells, which frequently display defective cell cycle check-point control. Healthy cells, by contrast, become quiescent and remain viable under arginine restriction, displaying full recovery upon return to arginine-rich conditions. The use of arginase therapy to restrict available arginine for selectively targeting malignant cells is currently under investigation in human clinical trials. However, the suitability of this approach for veterinary uses is unexplored. As a prelude to in vivo studies in canine malignancies, we examined the in vitro effects of arginine-deprivation on canine lymphoid and osteosarcoma cell lines. Two lymphoid and 2 osteosarcoma cell lines were unable to recover following 6 days of arginine deprivation, but all remaining cell lines displayed full recovery upon return to arginine-rich culture conditions. These remaining cell lines all proved susceptible to cell death following the addition of arginase to the cultures. The lymphoid lines were particularly sensitive to arginase, becoming unrecoverable after just 3 days of treatment. Two of the osteosarcoma lines were also susceptible over this time-frame; however the other 3 lines required 6-8 days of arginase treatment to prevent recovery. In contrast, adult progenitor cells from the bone marrow of a healthy dog were able to recover fully following 9 days of culture in arginase. Over 3 days in culture, arginase was more effective than asparaginase in inducing the death of lymphoid lines. These results strongly suggest that short-term arginase treatment warrants further investigation as a therapy for lymphoid malignancies and osteosarcomas in dogs. PMID:23365669

  18. Where Are Socioeconomically Deprived Immigrants Located in Chile? A Spatial Analysis of Census Data Using an Index of Multiple Deprivation from the Last Three Decades (1992-2012)

    PubMed Central

    2016-01-01

    Introduction and Purpose of the Study Immigrants in Chile have diverse characteristics and include socioeconomically deprived populations. The location of socioeconomically deprived immigrants is important for the development of public policy intelligence at the local and national levels but their areas of residence have not been mapped in Chile. This study explored the spatial distribution of socioeconomic deprivation among immigrants in Chile, 1992–2012, and compared it to the total population. Material and Methods Areas with socioeconomically deprived populations were identified with a deprivation index which we developed modelled upon the Index of Multiple Deprivation (IMD) for England. Our IMD was based upon the indicators of unemployment, low educational level (primary) and disability from Census data at county level for the three decades 1992, 2002 and 2012, for 332, 339 and 343 counties respectively. We developed two versions of the IMD one based on disadvantage among the total population and another focused upon the circumstances of immigrants only. We generated a spatial representation of the IMD using GIS, for the overall IMD score and for each dimension of the index, separately. We also compared the immigrants´ IMD to the total population´s IMD using Pearson´s correlation test. Results Results showed that socioeconomically deprived immigrants tended to be concentrated in counties in the northern and central area of Chile, in particular within the Metropolitan Region of Santiago. These were the same counties where there was the greatest concentration of socioeconomic deprivation for the total population during the same time periods. Since 1992 there have been significant change in the location of the socioeconomically deprived populations within the Metropolitan Region of Santiago with the highest IMD scores for both the total population and immigrants becoming increasingly concentrated in the central and eastern counties of the Region. Conclusion

  19. Oligometastatic prostate cancer: Metastases-directed therapy?

    PubMed

    Van Poppel, Hein; De Meerleer, Gert; Joniau, Steven

    2016-09-01

    Since the introduction of anatomical and functional imaging with multiparametric magnetic resonance imaging and choline or prostate-specific membrane antigen positron emission tomography-computed tomography, we are able to diagnose a previously unknown disease, the oligometastatic prostate cancer after local therapy. Reports on surgical and radiation treatment for low-volume metastatic recurrence have shown promising results, with definitive cure in few but a relevant delay of androgen-deprivation therapy with both treatment methods. Obviously, these results need to be validated with prospective randomised data. PMID:27547457

  20. Cardiovascular, Inflammatory and Metabolic Consequences of Sleep Deprivation

    PubMed Central

    Mullington, Janet M.; Haack, Monika; Toth, Maria; Serrador, Jorge; Meier-Ewert, Hans

    2009-01-01

    That insufficient sleep is associated with poor attention and performance deficits is becoming widely recognized. Fewer people are aware that chronic sleep complaints in epidemiological studies have also been associated with an increase in overall mortality and morbidity. This article summarizes findings of known effects of insufficient sleep on cardiovascular risk factors including blood pressure, glucose metabolism, hormonal regulation and inflammation with particular emphasis on experimental sleep loss, using models of total and partial sleep deprivation, in healthy individuals who normally sleep in the range of 7-8 hours and have no sleep disorders. These studies show that insufficient sleep alters established cardiovascular risk factors in a direction that is known to increase the risk of cardiac morbidity. PMID:19110131

  1. Detrimental role of prolonged sleep deprivation on adult neurogenesis

    PubMed Central

    Fernandes, Carina; Rocha, Nuno Barbosa F.; Rocha, Susana; Herrera-Solís, Andrea; Salas-Pacheco, José; García-García, Fabio; Murillo-Rodríguez, Eric; Yuan, Ti-Fei; Machado, Sergio; Arias-Carrión, Oscar

    2015-01-01

    Adult mammalian brains continuously generate new neurons, a phenomenon called adult neurogenesis. Both environmental stimuli and endogenous factors are important regulators of adult neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and adult neurogenesis in brain function, such as learning, memory, and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on adult neurogenesis. PMID:25926773

  2. Detrimental role of prolonged sleep deprivation on adult neurogenesis.

    PubMed

    Fernandes, Carina; Rocha, Nuno Barbosa F; Rocha, Susana; Herrera-Solís, Andrea; Salas-Pacheco, José; García-García, Fabio; Murillo-Rodríguez, Eric; Yuan, Ti-Fei; Machado, Sergio; Arias-Carrión, Oscar

    2015-01-01

    Adult mammalian brains continuously generate new neurons, a phenomenon called adult neurogenesis. Both environmental stimuli and endogenous factors are important regulators of adult neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and adult neurogenesis in brain function, such as learning, memory, and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on adult neurogenesis. PMID:25926773

  3. Regeneration, relocation and health behaviours in deprived communities.

    PubMed

    Kearns, Ade; Mason, Phil

    2015-03-01

    In the UK, recent regeneration programmes have aimed to improve the health of those who remain in their neighbourhood (Remainers) and those who are relocated (Outmovers); thus, as part of the 10-year GoWell study (2006-2015) of the effects of demolition, rebuilding and housing improvements on residents and communities, we examined associations of health behaviours with residential conditions and location status in deprived neighbourhoods of Glasgow. Better internal dwelling conditions were associated with several better health behaviours; in relation to neighbourhood conditions, the results were more mixed. Outmovers often exhibited worse health behaviours than Remainers, perhaps because environmental and social conditions were little altered by relocation, and because personal support mechanisms were missing. Health behaviours were relatively good among Remainers, indicating that in situ changes might stimulate life-changing improvements, but relocation less so. PMID:25618564

  4. Sleep deprivation of working adolescents--a hidden work hazard.

    PubMed

    Teixeira, Liliane R; Fischer, Frida M; Lowden, Arne

    2006-08-01

    This manuscript discusses the sleep deprivation of adolescents and young workers and its impact on their work and learning. Several studies have shown that working adolescents wake up earlier, have a shorter nocturnal sleep duration and a higher level of sleepiness during wake time during the week than nonworking students do. These studies indicate that working students may have their learning ability negatively affected by being tired and sleepy. Therefore, on the basis of these results, the authors recommend that educational programs geared to sleep hygiene should be one of the priorities of the curriculum. At the same time, the workhours of teenagers should be shortened in order to allow them to work and study during daytime and to have enough time at night for leisure and rest. These recommendations would improve the quality of life of the population that already is or will soon be participating in the job market. PMID:16932831

  5. Pathophysiology of Benign Prostatic Hyperplasia: Insights From Medical Therapy for the Disease

    PubMed Central

    Lepor, Herbert

    2009-01-01

    The medical treatment of benign prostatic hyperplasia (BPH) has its roots in the early 1970s. During this era, the first clinical trials investigating α-blockade and androgen deprivation therapy were reported for men with clinical BPH. The observation that clinical BPH was improved following administration of both α-blockers and androgen deprivation therapy supported the evolving paradigm that clinical BPH resulted from dynamic and static pathways. During the past several decades, the evolution of α-blockers for the treatment of BPH has been impacted by innovations targeted to simplify the administration and improve tolerability while maintaining their effectiveness. PMID:20126609

  6. Myocardium proteome remodelling after nutritional deprivation of methyl donors.

    PubMed

    Martinez, Emilie; Gérard, Nicolas; Garcia, Maira M; Mazur, Andrzej; Guéant-Rodriguez, Rosa-Maria; Comte, Blandine; Guéant, Jean-Louis; Brachet, Patrick

    2013-07-01

    Methyl donor (MD: folate, vitamin B12 and choline) deficiency causes hyperhomocysteinemia, a risk factor for cardiovascular diseases. However, the mechanisms of the association between MD deficiency, hyperhomocysteinemia, and cardiomyopathy remain unclear. Therefore, we performed a proteomic analysis of myocardium of pups from rat dams fed a MD-depleted diet to understand the impact of MD deficiency on heart at the protein level. Two-dimension gel electrophoresis and mass spectrometry-based analyses allowed us to identify 39 proteins with significantly altered abundance in MD-deficient myocardium. Ingenuity Pathway Analysis showed that 87% of them fitted to a single protein network associated with developmental disorder, cellular compromise and lipid metabolism. Concurrently increased protein carbonylation, the major oxidative post-translational protein modification, could contribute to the decreased abundance of many myocardial proteins after MD deficiency. To decipher the effect of MD deficiency on the abundance of specific proteins identified in vivo, we developed an in vitro model using the cardiomyoblast cell line H9c2. After a 4-day exposure to a MD-deprived (vs. complete) medium, cells were deficient of folate and vitamin B12, and released abnormal amounts of homocysteine. Western blot analyses of pup myocardium and H9c2 cells yielded similar findings for several proteins. Of specific interest is the result showing increased and decreased abundances of prohibitin and α-crystallin B, respectively, which underlines mitochondrial injury and endoplasmic reticulum stress within MD deficiency. The in vitro findings validate the MD-deficient H9c2 cells as a relevant model for studying mechanisms of the early metabolic changes occurring in cardiac cells after MD deprivation. PMID:23318136

  7. Relation between parasuicide, suicide, psychiatric admissions, and socioeconomic deprivation.

    PubMed Central

    Gunnell, D. J.; Peters, T. J.; Kammerling, R. M.; Brooks, J.

    1995-01-01

    OBJECTIVE--To examine the relations between parasuicide, suicide, psychiatric inpatient admissions, and socioeconomic deprivation. DESIGN--Ecological analysis with data from routine information systems and the 1991 census. SETTING--24 localities in the area covered by the Bristol and District Health Authority (population 817,000), consisting of aggregations of neighbouring wards, with an average population of 34,000. SUBJECTS--6089 subjects aged over 10 years admitted to hospital after parasuicide between April 1990 and March 1994; 997 suicides occurring 1982-91; 4763 subjects aged 10-64 years admitted with acute psychiatric illness between April 1990 and March 1994. RESULTS--Localities varied significantly in standardised admission ratios for parasuicide and standardised mortality ratios for suicide (P < 0.001). Spearman's rank correlation coefficient between the standardised mortality ratio for suicide and standardised admission ratio for parasuicide was 0.73 (95% confidence interval 0.46 to 0.88). Correlation between parasuicide and Townsend score was 0.86 (0.70 to 0.94) and between suicide and Townsend score 0.73 (0.46 to 0.88). The partial correlation coefficient between suicide and parasuicide after the Townsend score was adjusted for was 0.29 (-0.13 to 0.62). The correlation between standardised admission ratio for parasuicide and standardised admission ratio for psychiatric illness was 0.76 (0.51 to 0.89) and between standardised mortality ratio for suicide and standardised admission ratio for psychiatric illness was 0.72 (0.45 to 0.87). CONCLUSION--A strong ecological association exists between suicide and parasuicide, with socioeconomic deprivation accounting for much of this relation. This strong association provides supporting evidence for the importance of social policy measures in attaining Health of the Nation targets on mental health. PMID:7627035

  8. Intravenous immunoglobulin transfusion in colostrum-deprived dairy calves.

    PubMed

    Boccardo, A; Belloli, A; Biffani, S; Locatelli, V; Dall'Ara, P; Filipe, J; Restelli, I; Proverbio, D; Pravettoni, D

    2016-03-01

    Immunoglobulin transfusion is employed in the management of the failure of passive transfer (FPT). The aim of this study was to investigate the dose of immunoglobulin G (IgG) needed to reach a protective concentration (>10 g/L) in colostrum-deprived dairy calves. Twenty-eight Holstein Friesian newborn male calves were randomly assigned to either a control group (CG) or a treatment group (PG). Calves in the CG received 4 L of high quality colostrum within 12 h of birth. Calves in the PG received 62.7 ± 3.1 g of IgG IV in 2.6 ± 0.3 L of plasma within 6 h after birth. Serum immunoglobulin G (sIgG) and serum total protein (sTP) concentrations were assayed before and after (24 h, 72 h and 1 week after birth) plasma transfusion or colostrum ingestion. Serum (s) IgG and sTP concentrations increased in both groups throughout the period of observation. Mean sIgG and sTP concentrations after colostrum ingestion or plasma transfusion were higher in the CG than in the PG (P <0.01). Nine treated calves developed diarrhoea during the study and four were humanely euthanased due to progressive clinical deterioration. None of the calves in the CG showed signs of disease or died during the study. The dose of IgG used in this trial effectively provided an adequate sIgG concentration in colostrum-deprived calves (>10 g/L). Calves in the CG had significantly lower morbidity and mortality rates compared to those in the PG, suggesting that plasma transfusion alone is ineffective in providing complete protection against neonatal disease. PMID:26831168

  9. Effects of Fatigue and Sleep Deprivation on Microvascular Anastomoses.

    PubMed

    Basaran, Karaca; Mercan, Ebru Sen; Aygit, Ahmet Cemal

    2015-06-01

    Previous studies have investigated the effects of various human-based factors, such as tremor, exercise, and posture, on microsurgical performance. In this study, the authors investigated the effects of sleep deprivation and fatigue on microsurgery. A total of 48 Wistar Hannover rats were divided into 3 groups (16 anastomoses in each group) to be operated on at 3 different times: in the morning at 08:00 hours (group I), at night on the same day (01:00 h, group II), and the next morning at 09:00 hours (group III) following a night with no sleep. The blindly evaluated parameters were anastomotic times, error score (ES), global rating scale (GRS), autopsy scores (ASs), and patency. There was progressive decrease in the anastomosis times between the groups (P > 0.05). The patency rates were 93% in group I, 81% in group II, and 81% in group III (P > 0.05). The ES (P < 0.01), AS (P < 0.001), and GRS (P < 0.001) revealed significant results. Comparison between the groups showed that other than the anastomosis time, the night group (group II) showed a significant drop when compared with the preceding morning group (group I) (ES P < 0.01, AS P < .001, and GRS P < 0.001). In most of the parameters, the errors occurred with fatigue after the day and reached a maximum at the end of the day (group II). This study provides valuable data that might have significant medicolegal implications for controversial issues. More studies, however, including multiple surgeons with different experience levels, might be required to fully elucidate the overall effects of fatigue and sleep deprivation on microsurgery. PMID:26080191

  10. Deprivation-related and use-dependent plasticity go hand in hand

    PubMed Central

    Makin, Tamar R; Cramer, Alona O; Scholz, Jan; Hahamy, Avital; Henderson Slater, David; Tracey, Irene; Johansen-Berg, Heidi

    2013-01-01

    Arm-amputation involves two powerful drivers for brain plasticity—sensory deprivation and altered use. However, research has largely focused on sensory deprivation and maladaptive change. Here we show that adaptive patterns of limb usage after amputation drive cortical plasticity. We report that individuals with congenital or acquired limb-absence vary in whether they preferentially use their intact hand or residual arm in daily activities. Using fMRI, we show that the deprived sensorimotor cortex is employed by whichever limb individuals are over-using. Individuals from either group that rely more on their intact hands (and report less frequent residual arm usage) showed increased intact hand representation in the deprived cortex, and increased white matter fractional anisotropy underlying the deprived cortex, irrespective of the age at which deprivation occurred. Our results demonstrate how experience-driven plasticity in the human brain can transcend boundaries that have been thought to limit reorganisation after sensory deprivation in adults. DOI: http://dx.doi.org/10.7554/eLife.01273.001 PMID:24220510

  11. Sleep deprivation selectively disrupts top-down adaptation to cognitive conflict in the Stroop test.

    PubMed

    Gevers, Wim; Deliens, Gaetane; Hoffmann, Sophie; Notebaert, Wim; Peigneux, Philippe

    2015-12-01

    Sleep deprivation is known to exert detrimental effects on various cognitive domains, including attention, vigilance and working memory. Seemingly at odds with these findings, prior studies repeatedly failed to evidence an impact of prior sleep deprivation on cognitive interference in the Stroop test, a hallmark paradigm in the study of cognitive control abilities. The present study investigated further the effect of sleep deprivation on cognitive control using an adapted version of the Stroop test that allows to segregate top-down (attentional reconfiguration on incongruent items) and bottom-up (facilitated processing after repetitions in responses and/or features of stimuli) components of performance. Participants underwent a regular night of sleep or a night of total sleep deprivation before cognitive testing. Results disclosed that sleep deprivation selectively impairs top-down adaptation mechanisms: cognitive control no longer increased upon detection of response conflict at the preceding trial. In parallel, bottom-up abilities were found unaffected by sleep deprivation: beneficial effects of stimulus and response repetitions persisted. Changes in vigilance states due to sleep deprivation selectively impact on cognitive control in the Stroop test by affecting top-down, but not bottom-up, mechanisms that guide adaptive behaviours. PMID:26173051

  12. A Philosophical Concept of Deprivation and Its Use in the Attachment-Focused Treatment of Violence

    PubMed Central

    Pârvan, Alexandra

    2015-01-01

    Theories in both contemporary psychotherapy and ancient philosophy associate deprivation with wrongdoing and suffering, but operate with different under-standings of deprivation. The article will focus on two concepts of deprivation, one psychological and the other one ontological, as advanced by Bowlby in attachment theory, and Augustine of Hippo (354–430 CE). In attachment theory deprivation is something one suffers as a result of the others’ actions (receipt of insensitive caregiving in early childhood); it has neuropsychological effects, it relates to violent behaviour later in life, and it is therapeutically treated mainly by emotional sensory work directed at attaining self-regulation. Understanding deprivation as Augustine does (i.e., diminishment of a being’s inner unity and order caused by one’s exercise of will) introduces a distinctive philosophical view on formation and can inform a type of reflective-behavioural work centred on forming impaired volitional and emotional capacities, and on reclaiming agency and responsibility both for what can be called self-deprivation and for ways to counter deprivation in offenders and victims. PMID:26549927

  13. Income deprivation and mental well-being: the role of non-cognitive skills.

    PubMed

    Blázquez Cuesta, Maite; Budría, Santiago

    2015-04-01

    We show that the positive relation between income deprivation and mental health is affected by an individual's non-cognitive skills. Income deprivation is operationalized as the Yitzhaki index, i.e., as a function of the sum of income differences between an individual and others in her reference group who are more affluent. Non-cognitive skills are extracted from a Locus of Control questionnaire and the Big Five Inventory, a self-report measurement of an individual in regard to five aspects of personality: conscientiousness, neuroticism, extraversion, agreeableness and open-mindedness. The results, based on the 2002-2010 waves of the German Socio-Economic Panel dataset (SOEP), show that deprivation is negative and significantly related with mental health. However, neurotic individuals are more deprivation-sensitive than are others. Compared to the mean effect, a one standard deviation rise in neuroticism is associated with a deprivation effect that is 36.6% and 51.9% larger among men and women, respectively. Although to a lesser extent, extraverted men and conscientious women are also found to be more deprivation-sensitive than are others, the corresponding figures being 31.1% and 45.9%, respectively. These findings suggest that personality differences should be taken into account in the design of policies, practices and initiatives aimed at alleviating the well-being costs of income deprivation. PMID:25590947

  14. Effects of sleep deprivation and exercise on cognitive, motor performance and mood.

    PubMed

    Scott, Jonathon P R; McNaughton, Lars R; Polman, Remco C J

    2006-02-28

    This study examined the effect of 30 h of sleep deprivation and intermittent physical exercise, on both cognitive and psychomotor function as well subjective ratings of mood. Six subjects with the following physical characteristics participated in the study (Mean +/- S.D.): age 22 +/- 0.3 years, height 180 +/- 5 cm, body mass: 77 +/- 5 kg, VO2peak 44 +/- 5 ml kg(-1) min(-1). Three subjects engaged in normal sedentary activities while three others cycled on a cycle ergometer at 50% VO2peak for 20 min out of every 2 h during 30 h of sleep deprivation. One week later sleep deprivation was repeated with a cross over of subjects. Every 4 h, subjects completed simple and two-choice reaction time tasks at both rest and during exercise, a computerized tracking task, a number cancellation task, and an assessment of subjective mood state as measured by the POMS questionnaire. A 3 x 4 repeated measures ANOVA revealed that resting but not exercising reaction times were significantly slower with sleep deprivation. Sleep deprivation was also associated with significantly greater negative disturbances to subjective vigour, fatigue and depression assessed by the Profile of Mood States questionnaire. Compared to those who have been deprived of sleep alone, individuals that performed 5 h of intermittent moderate exercise during 30 h of sleep deprivation appeared to be more vulnerable to negative mood disturbances and impairment in reaction times. This could result in greater risk of accident due to a reduced capacity to respond quickly. PMID:16403541

  15. Effects of mental resilience on neuroendocrine hormones level changes induced by sleep deprivation in servicemen.

    PubMed

    Sun, Xinyang; Dai, Xuyan; Yang, Tingshu; Song, Hongtao; Yang, Jialin; Bai, Jing; Zhang, Liyi

    2014-12-01

    The aim of this study was to investigate the effects of mental resilience on the changes of serum rennin, angiotensin, and cortisol level induced by sleep deprivation in servicemen. By random cluster sampling, a total of 160 servicemen, aged from 18 to 30, were selected to undergo 24-hour total sleep deprivation and administered the military personnel mental resilience scale after the deprivation procedure. The sleep deprivation procedure started at 8 a.m. on Day 8 and ended at 8 a.m. on Day 9 after 7 days of normal sleep for baseline preparation. Blood samples were drawn from the 160 participants at 8 a.m. respectively on Day 8 and Day 9 for hormonal measurements. All blood samples were analyzed using radioimmunoassay. As hypothesized, serum rennin, angiotensin II, and cortisol level of the participants after sleep deprivation were significantly higher than those before (P < 0.05). The changes of serum rennin and cortisol in the lower mental resilience subgroup were significantly greater (P < 0.05); problem-solving skill and willpower were the leading influence factors for the increases of serum rennin and cortisol respectively induced by sleep deprivation. We conclude that mental resilience plays a significant role in alleviating the changes of neurohormones level induced by sleep deprivation in servicemen. PMID:24633577

  16. [Blood biochemical changes in maternally deprived children and their emotional status].

    PubMed

    Gogberashvili, K Ia; Gagoshidze, M V; Pagava, K I

    2011-01-01

    Environmental rearing conditions during the neonatal period are critical for the establishment of neurobiological factors controlling behavior and stress responsiveness. Early maternal deprivation in animals consisting of a single 24-h maternal deprivation episode during early neonatal life has been proposed as an animal model for certain psychopathologies including anxiety, depression and schizophrenic-related disorders. The aim of the present research was to show the mechanisms how the early maternal deprivation in humans influences the emotional status of children. To understand the effects of early deprivation on the regulation of the hypothalamic-pituitary-adrenal axis of children following social interactions, we examined the blood neurotransmitters levels (Norepinefrin NA; Dofamin DF; Serotonin SE) in a group of healthy institutionalized children at age from 6 to 36 months from Tbilisi Infant's House. A group of healthy children of the same age from Mother & child shelters formed the control group. Emotional status was assessed by Leusher's Color Test in a group of healthy institutionalized children at age from 3 to 6 years from Tskneti Orphanage. Institutionalized children showed elevations in blood NE and decreased SE and DF concentrations in comparison with non deprived children's blood. The higher was percentage of children with high level of anxiety in the group of children from orphanage than in the children with family care. The results suggest that early maternal deprivation may contribute to long-term regulatory problems of the stress-responsive system that may be resulted in altered emotionality and behavior in deprived children. PMID:21873754

  17. Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction

    PubMed Central

    Zhao, Wei; Wang, Jun; Bi, Weina; Ferruzzi, Mario; Yemul, Shrishailam; Freire, Daniel; Mazzola, Paolo; Ho, Lap; Dubner, Lauren; Pasinetti, Giulio Maria

    2016-01-01

    Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction. PMID:26235983

  18. Maternal deprivation of rat pups increases clinical symptoms of experimental autoimmune encephalomyelitis at adult age.

    PubMed

    Teunis, Marc A T; Heijnen, Cobi J; Sluyter, Frans; Bakker, Joost M; Van Dam, Anne-Marie M W; Hof, Maleen; Cools, Alexander R; Kavelaars, Annemieke

    2002-12-01

    Maternal deprivation of neonatal animals has been shown to induce long-lasting changes in the reactivity of the neuroendocrine system. The aim of the present study was to investigate whether maternal deprivation also affects susceptibility to immune-mediated diseases such as experimental autoimmune encephalomyelitis (EAE) in adult life. To this end, 9-day-old rat pups were subjected to a short-lasting maternal deprivation for a period of 24 h. At the age of 8 weeks, we induced EAE in these rats by immunization with myelin basic protein (MBP) in complete Freund's adjuvant. Our data demonstrate that short-lasting maternal deprivation induces a marked increase in the severity of EAE in the animals in later life. The histopathological evaluation of spinal cord and cerebellum corresponded with the observed differences in clinical symptoms of EAE. Moreover, neonatal maternal deprivation affects macrophage functioning at adult age. In contrast, no differences were observed in in vitro mitogen- and MBP-induced cytokine production by splenocytes. LPS-induced corticosterone release did not differ either between maternally deprived and control animals. We conclude that short-lasting neonatal maternal deprivation of rat pups has long-lasting consequences for macrophage activity and for susceptibility to the inflammatory autoimmune disease EAE. PMID:12446005

  19. Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction.

    PubMed

    Zhao, Wei; Wang, Jun; Bi, Weina; Ferruzzi, Mario; Yemul, Shrishailam; Freire, Daniel; Mazzola, Paolo; Ho, Lap; Dubner, Lauren; Pasinetti, Giulio Maria

    2015-10-01

    Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction. PMID:26235983

  20. Food Deprivation, Body Weight Loss and Anxiety-Related Behavior in Rats.

    PubMed

    Dietze, Silke; Lees, Katarina R; Fink, Heidrun; Brosda, Jan; Voigt, Jörg-Peter

    2016-01-01

    In behavioral studies, food deprivation protocols are routinely used to initiate or maintain motivational states that are required in a particular test situation. However, there is limited evidence as to when food deprivation compromises animal welfare. This study investigated the effects of different lengths of food deprivation periods and restricted (fixed-time) feeding on body weight loss as well as anxiety-related and motivated behavior in 5-6 month old male and female Wistar rats. The observed body weight loss was not influenced by sex and ranged between 4% (16 h deprivation) to approximately 9% (fixed-time feeding). Despite significant body weight loss in all groups, the motivation to eat under the aversive test conditions of the modified open field test increased only after 48 h of food deprivation. Long-lasting effects on anxiety as measured in the elevated plus maze test 24 h after refeeding have not been observed, although fixed-time feeding could possibly lead to a lasting anxiogenic effect in female rats. Overall, female rats showed a more anxiolytic profile in both tests when compared to male rats. Despite these sex differences, results suggest that food deprivation is not always paralleled by an increased motivation to feed in a conflict situation. This is an important finding as it highlights the need for tailored pilot experiments to evaluate the impact of food deprivation protocols on animals in regard to the principles of the 3Rs introduced by Russell and Burch. PMID:26751481

  1. Rural Area Deprivation and Hospitalizations Among Children for Ambulatory Care Sensitive Conditions.

    PubMed

    Hale, Nathan; Probst, Janice; Robertson, Ashley

    2016-06-01

    This study examined the intersection of rurality and community area deprivation using a nine-state sample of inpatient hospitalizations among children (<18 years of age) from 2011. One state from each of the nine US census regions with substantial rural representation and varying degrees of community vulnerability was selected. An area deprivation index was constructed and used in conjunction with rurality to examine differences in the rate of ACSC hospitalizations among children in the sample states. A mixed model with both fixed and random effects was used to test influence of rurality and area deprivation on the odds of a pediatric hospitalization due to an ACSC within the sample. Of primary interest was the interaction of rurality and area deprivation. The study found rural counties are disproportionality represented among the most deprived. Within the least deprived counties, the likelihood of an ACSC hospitalization was significantly lower in rural than among their urban counterparts. However, this rural advantage declines as the level of deprivation increases, suggesting the effect of rurality becomes more important as social and economic advantage deteriorates. We also found ACSC hospitalization to be much higher among racial/ethnic minority children and those with Medicaid or self-pay as an anticipated source of payment. These findings further contribute to the existing body of evidence documenting racial/ethnic disparities in important health related outcomes. PMID:26516019

  2. Do neighborhood socioeconomic deprivation and low social cohesion predict coronary calcification?: the CARDIA study.

    PubMed

    Kim, Daniel; Diez Roux, Ana V; Kiefe, Catarina I; Kawachi, Ichiro; Liu, Kiang

    2010-08-01

    Growing evidence suggests that neighborhood characteristics may influence the risk of coronary heart disease. No studies have yet explored associations of neighborhood attributes with subclinical atherosclerosis in younger adult populations. Using data on 2,974 adults (1,699 women, 1,275 men) aged 32-50 years in 2000 from the Coronary Artery Disease Risk Development in Young Adults (CARDIA) Study and 2000 US Census block-group-level data, the authors estimated multivariable-adjusted associations of neighborhood socioeconomic deprivation and perceived neighborhood cohesion with odds of coronary artery calcification (CAC) 5 years later. Among women, the quartiles of highest neighborhood deprivation and lowest cohesion were associated with higher odds of CAC after adjustment for individual-level demographic and socioeconomic factors (for deprivation, odds ratio = 2.49, 95% confidence interval: 1.22, 5.08 (P for trend = 0.03); for cohesion, odds ratio = 1.87, 95% confidence interval: 1.10, 3.16 (P for trend = 0.02)). Associations changed only slightly after adjustment for behavioral, psychosocial, and biologic factors. Among men, neither neighborhood deprivation nor cohesion was related to CAC. However, among men in deprived neighborhoods, low cohesion predicted higher CAC odds (for interaction between neighborhood deprivation and cohesion, P = 0.03). This study provides evidence on associations of neighborhood deprivation and cohesion with CAC in younger, asymptomatic adults. Neighborhood attributes may contribute to subclinical atherosclerosis. PMID:20610467

  3. Do Neighborhood Socioeconomic Deprivation and Low Social Cohesion Predict Coronary Calcification?

    PubMed Central

    Kim, Daniel; Diez Roux, Ana V.; Kiefe, Catarina I.; Kawachi, Ichiro; Liu, Kiang

    2010-01-01

    Growing evidence suggests that neighborhood characteristics may influence the risk of coronary heart disease. No studies have yet explored associations of neighborhood attributes with subclinical atherosclerosis in younger adult populations. Using data on 2,974 adults (1,699 women, 1,275 men) aged 32–50 years in 2000 from the Coronary Artery Disease Risk Development in Young Adults (CARDIA) Study and 2000 US Census block-group-level data, the authors estimated multivariable-adjusted associations of neighborhood socioeconomic deprivation and perceived neighborhood cohesion with odds of coronary artery calcification (CAC) 5 years later. Among women, the quartiles of highest neighborhood deprivation and lowest cohesion were associated with higher odds of CAC after adjustment for individual-level demographic and socioeconomic factors (for deprivation, odds ratio = 2.49, 95% confidence interval: 1.22, 5.08 (P for trend = 0.03); for cohesion, odds ratio = 1.87, 95% confidence interval: 1.10, 3.16 (P for trend = 0.02)). Associations changed only slightly after adjustment for behavioral, psychosocial, and biologic factors. Among men, neither neighborhood deprivation nor cohesion was related to CAC. However, among men in deprived neighborhoods, low cohesion predicted higher CAC odds (for interaction between neighborhood deprivation and cohesion, P = 0.03). This study provides evidence on associations of neighborhood deprivation and cohesion with CAC in younger, asymptomatic adults. Neighborhood attributes may contribute to subclinical atherosclerosis. PMID:20610467

  4. Benefits of intermittent/continuous androgen deprivation in patients with advanced prostate cancer

    PubMed Central

    MURESANU, HORIA

    2016-01-01

    Background and aims In 1941 Huggins described the effect of castration on prostate cancer. gonadotropin-releasing hormone (GNRH) analogues were introduced in 1985. Complete androgen blockade (association of GNRH analogue with antiandrogen) was introduced by Fernand Labrie to achieve suppression of suprarenal testosterone. Long time androgen deprivation lead to androgen independence of the prostate cancer cell. Our principal aim was to demonstrate longer survival rates on prostate cancer patients with intermittent androgen deprivation. Methods 82 patients in the Urology Department of Vasile Goldis West University Arad were included into two groups, with continuous and intermittent androgen deprivation. Treatment efficiency was assessed by the level of testosterone and PSA. Adverse events (AE) and serious adverse events were reported according to Common Terminology Criteria of Adverse Events (CTCAE) of the National Cancer Institute (NCI). Results Evolution towards castrate resistant prostate cancer: 12.5% from the intermittent androgen deprivation group and 23.8% from the continuous androgen deprivation group Mortality rate: 15% of patients from the intermittent androgen deprivation group; 19% of patients from the continuous androgen deprivation group Conclusions Better quality of life (Qol) in periods without treatment due to testosteron recovery; Less AE’s and metabolic syndrome (MS) related complications; Better survival and longer time of disease control and Cost reduction. PMID:27547063

  5. Progress and controversies: Radiation therapy for prostate cancer.

    PubMed

    Martin, Neil E; D'Amico, Anthony V

    2014-01-01

    Radiation therapy remains a standard treatment option for men with localized prostate cancer. Alone or in combination with androgen-deprivation therapy, it represents a curative treatment and has been shown to prolong survival in selected populations. In this article, the authors review recent advances in prostate radiation-treatment techniques, photon versus proton radiation, modification of treatment fractionation, and brachytherapy-all focusing on disease control and the impact on morbidity. Also discussed are refinements in the risk stratification of men with prostate cancer and how these are better for matching patients to appropriate treatment, particularly around combined androgen-deprivation therapy. Many of these advances have cost and treatment burden implications, which have significant repercussions given the prevalence of prostate cancer. The discussion includes approaches to improve value and future directions for research. PMID:25234700

  6. [Pathophysiology and therapy of castration-resistant prostate cancer].

    PubMed

    Merseburger, A S; Kuczyk, M A; Wolff, J M

    2013-02-01

    Advanced prostate cancer that progresses under androgen deprivation therapy has long been thought to be refractory to further hormonal treatment. The identification of the mechanism of cancer cells has revolutionized this understanding. Today it is known that castration-resistant prostate cancer (CRPC) still receives signals through the androgen receptor transduction pathways and furthermore is sensitive to hormone therapy. New substances, such as abiraterone, enzalutamide (MDV3100) and TAK 700 target these mechanisms of resistance of cancer cells, stop testosterone production and show not only better tolerance but also effective antitumor activity. Due to the heterogeneity of tumors with cells in varying states of differentiation, the treatment of CRPC with androgen deprivation therapy remains a cornerstone of disease management. To what extent the experimental findings and the recommendations in the guidelines are put into practice was the subject of a survey among urologists analyzing their treatment strategies with CRPC patients. PMID:23160609

  7. Discriminant and criterion-related validity of a relative deprivation scale in a merger and acquisition context.

    PubMed

    Lee, Dongseop; Cho, Bongsoon; Seo, Jeongil; Lee, Khan-Pyo; Choi, Jang-Ho

    2014-02-01

    This study examined the discriminant and criterion-related validity of the Relative Deprivation Scale. The data were collected from 151 Korean employees who had recently experienced a merger and acquisition. The results of confirmatory factor analysis revealed that the two dimensions of relative deprivation (egoistic and fraternal relative deprivation) are clearly distinguishable from other conceptually related variables, such as negative affectivity, resistance to change, overall job dissatisfaction, and distributive justice. In addition, egoistic relative deprivation made a unique incremental contribution to explaining employee turnover intention beyond the contribution of conceptually related variables, while fraternal relative deprivation did not. PMID:24765711

  8. Inhibition of scleral proteoglycan synthesis blocks deprivation-induced axial elongation in chicks.

    PubMed

    Rada, J A; Johnson, J M; Achen, V R; Rada, K G

    2002-02-01

    A specific inhibitor of proteoglycan synthesis was administered to chicks undergoing the development of form deprivation myopia in order to test the hypothesis that increases in proteoglycan synthesis are responsible for normal and/or deprivation-induced ocular elongation in chicks. Chicks undergoing monocular form deprivation were treated with p-nitrophenyl-beta-D-xylopyranoside (beta-xyloside) via i.p. injection every 8 hr for 5-11 days. Ocular measurements were made at the end of the experiment using high frequency A-scan ultrasound in conjunction with a LabView (v. 5.0) analysis program. Following ultrasound measurements, sclera were isolated and proteoglycans characterized by Sepharose CL-2B and Western blot analyses. Preliminary studies indicated that i.p. administration of beta-xyloside maximally inhibited sulfate incorporation into proteoglycans 8 hr after administration. Beta-xyloside treatment resulted in a significant reduction in the axial length, vitreous chamber depth, and rate of axial elongation of form deprived eyes as compared with form deprived eyes from vehicle treated chicks (P < 0.01, P < 0.05, P < 0.05, respectively). No significant differences were detected in anterior chamber depth, lens thickness, choroid thickness or retina thickness in form deprived eyes of beta-xyloside treated chicks as compared with that of vehicle controls. No significant differences were detected in contralateral non-deprived fellow eyes between beta-xyloside treated and vehicle treated chicks for any ocular measurement. Analysis of proteoglycans indicated that the xyloside treatment resulted in the accumulation of smaller proteoglycans due, in part, to the presence of underglycosylated aggrecan within the scleral matrix. These results indicate that interruption of normal scleral proteoglycan synthesis inhibits form deprivation-induced ocular elongation, supporting the hypothesis that scleral proteoglycan synthesis and accumulation are largely responsible for

  9. Sleep deprivation-induced multi-organ injury: role of oxidative stress and inflammation

    PubMed Central

    Periasamy, Srinivasan; Hsu, Dur-Zong; Fu, Yu-Hsuan; Liu, Ming-Yie

    2015-01-01

    Sleep deprivation affects all aspects of health. Adverse health effects by sleep deviation are still underestimated and undervalued in clinical practice and, to a much greater extent in monitoring human health. We hypothesized that sleep deprivation-induced mild organ injuries; oxidative stress and inflammation might play a crucial role in inducing multi-organ injury. Male C57BL/6J mice (n = 6-7) were sleep-deprived for 0-72 h using a modified multiple platform boxes method. Blood and tissue were collected. Liver, heart, kidney, lung, and pancreatic injuries were evaluated using biochemical and histological analyses. Glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), total billirubin (TBIL), creatine phosphokinase (CPK), creatine phosphokinase-myocardial band (CKMB), lactic dehydrogenase (LDH), creatinine (CRE), and blood urea nitrogen (BUN) were assayed in blood. Malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were measured. Histology revealed mild-to-moderate liver and lung injury in sleep-deprived mice. Sleep-deprived mice had significantly higher GOT, GPT, TBIL, CPK, CKMB, LDH, BUN, and α-amylase (AMYL) levels, which indicated liver, heart, kidney, and pancreatic injuries. Serum IL-1β at 24 h and IL-6 at 72 h were significantly higher in sleep-deprived than in control mice. Hepatic TNF-α and IL-1β were significantly higher, but IL-6 significantly lower in mice that had been sleep-deprived for 72 h. Sleep deprivation-mediated inflammation may be associated with mild to moderate multi-organ damage in mice. The implication of this study indicates sleep deprivation in humans may induce multi-organ injury that negatively affects cardiovascular and gastrointestinal health. PMID:26648820

  10. Sleep deprivation-induced multi-organ injury: role of oxidative stress and inflammation.

    PubMed

    Periasamy, Srinivasan; Hsu, Dur-Zong; Fu, Yu-Hsuan; Liu, Ming-Yie

    2015-01-01

    Sleep deprivation affects all aspects of health. Adverse health effects by sleep deviation are still underestimated and undervalued in clinical practice and, to a much greater extent in monitoring human health. We hypothesized that sleep deprivation-induced mild organ injuries; oxidative stress and inflammation might play a crucial role in inducing multi-organ injury. Male C57BL/6J mice (n = 6-7) were sleep-deprived for 0-72 h using a modified multiple platform boxes method. Blood and tissue were collected. Liver, heart, kidney, lung, and pancreatic injuries were evaluated using biochemical and histological analyses. Glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), total billirubin (TBIL), creatine phosphokinase (CPK), creatine phosphokinase-myocardial band (CKMB), lactic dehydrogenase (LDH), creatinine (CRE), and blood urea nitrogen (BUN) were assayed in blood. Malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 levels were measured. Histology revealed mild-to-moderate liver and lung injury in sleep-deprived mice. Sleep-deprived mice had significantly higher GOT, GPT, TBIL, CPK, CKMB, LDH, BUN, and α-amylase (AMYL) levels, which indicated liver, heart, kidney, and pancreatic injuries. Serum IL-1β at 24 h and IL-6 at 72 h were significantly higher in sleep-deprived than in control mice. Hepatic TNF-α and IL-1β were significantly higher, but IL-6 significantly lower in mice that had been sleep-deprived for 72 h. Sleep deprivation-mediated inflammation may be associated with mild to moderate multi-organ damage in mice. The implication of this study indicates sleep deprivation in humans may induce multi-organ injury that negatively affects cardiovascular and gastrointestinal health. PMID:26648820

  11. Area-level socioeconomic deprivation, nitrogen dioxide exposure, and term birth weight in New York City.

    PubMed

    Shmool, Jessie L C; Bobb, Jennifer F; Ito, Kazuhiko; Elston, Beth; Savitz, David A; Ross, Zev; Matte, Thomas D; Johnson, Sarah; Dominici, Francesca; Clougherty, Jane E

    2015-10-01

    Numerous studies have linked air pollution with adverse birth outcomes, but relatively few have examined differential associations across the socioeconomic gradient. To evaluate interaction effects of gestational nitrogen dioxide (NO2) and area-level socioeconomic deprivation on fetal growth, we used: (1) highly spatially-resolved air pollution data from the New York City Community Air Survey (NYCCAS); and (2) spatially-stratified principle component analysis of census variables previously associated with birth outcomes to define area-level deprivation. New York City (NYC) hospital birth records for years 2008-2010 were restricted to full-term, singleton births to non-smoking mothers (n=243,853). We used generalized additive mixed models to examine the potentially non-linear interaction of nitrogen dioxide (NO2) and deprivation categories on birth weight (and estimated linear associations, for comparison), adjusting for individual-level socio-demographic characteristics and sensitivity testing adjustment for co-pollutant exposures. Estimated NO2 exposures were highest, and most varying, among mothers residing in the most-affluent census tracts, and lowest among mothers residing in mid-range deprivation tracts. In non-linear models, we found an inverse association between NO2 and birth weight in the least-deprived and most-deprived areas (p-values<0.001 and 0.05, respectively) but no association in the mid-range of deprivation (p=0.8). Likewise, in linear models, a 10 ppb increase in NO2 was associated with a decrease in birth weight among mothers in the least-deprived and most-deprived areas of -16.2g (95% CI: -21.9 to -10.5) and -11.0 g (95% CI: -22.8 to 0.9), respectively, and a non-significant change in the mid-range areas [β=0.5 g (95% CI: -7.7 to 8.7)]. Linear slopes in the most- and least-deprived quartiles differed from the mid-range (reference group) (p-values<0.001 and 0.09, respectively). The complex patterning in air pollution exposure and deprivation

  12. Assessing Individual Differences in Adaptation to Extreme Environments: A 36-Hour Sleep Deprivation Study

    NASA Technical Reports Server (NTRS)

    Martinez, Jacqueline; Cowings, Patricia S.; Toscano, William B.

    2012-01-01

    In space, astronauts may experience effects of cumulative sleep loss due to demanding work schedules that can result in cognitive performance impairments, mood state deteriorations, and sleep-wake cycle disruption. Individuals who experience sleep deprivation of six hours beyond normal sleep times experience detrimental changes in their mood and performance states. Hence, the potential for life threatening errors increases exponentially with sleep deprivation. We explored the effects of 36-hours of sleep deprivation on cognitive performance, mood states, and physiological responses to identify which metrics may best predict fatigue induced performance decrements of individuals.

  13. Food Deprivation, Body Weight Loss and Anxiety-Related Behavior in Rats

    PubMed Central

    Dietze, Silke; Lees, Katarina R.; Fink, Heidrun; Brosda, Jan; Voigt, Jörg-Peter

    2016-01-01

    Simple Summary Food deprivation protocols are frequently used in behavioral studies. However, there is limited evidence as to when food deprivation compromises animal welfare. Regarding the refinement of experiments involving animals, this study investigated the effects of food deprivation on body weight loss and behavior in male and female rats. Sex difference in behavior and motivational state after food deprivation is the main finding of the study. The data highlights the need for tailored pilot experiments to evaluate the impact of food deprivation on animals with regard to the 3Rs principles (replacement, reduction, refinement) in animal science. Abstract In behavioral studies, food deprivation protocols are routinely used to initiate or maintain motivational states that are required in a particular test situation. However, there is limited evidence as to when food deprivation compromises animal welfare. This study investigated the effects of different lengths of food deprivation periods and restricted (fixed-time) feeding on body weight loss as well as anxiety-related and motivated behavior in 5–6 month old male and female Wistar rats. The observed body weight loss was not influenced by sex and ranged between 4% (16 h deprivation) to approximately 9% (fixed-time feeding). Despite significant body weight loss in all groups, the motivation to eat under the aversive test conditions of the modified open field test increased only after 48 h of food deprivation. Long-lasting effects on anxiety as measured in the elevated plus maze test 24 h after refeeding have not been observed, although fixed-time feeding could possibly lead to a lasting anxiogenic effect in female rats. Overall, female rats showed a more anxiolytic profile in both tests when compared to male rats. Despite these sex differences, results suggest that food deprivation is not always paralleled by an increased motivation to feed in a conflict situation. This is an important finding as it highlights

  14. Glutamine deprivation enhances antitumor activity of 3-bromopyruvate through the stabilization of monocarboxylate transporter-1.

    PubMed

    Cardaci, Simone; Rizza, Salvatore; Filomeni, Giuseppe; Bernardini, Roberta; Bertocchi, Fabio; Mattei, Maurizio; Paci, Maurizio; Rotilio, Giuseppe; Ciriolo, Maria Rosa

    2012-09-01

    Anticancer drug efficacy might be leveraged by strategies to target certain biochemical adaptations of tumors. Here we show how depriving cancer cells of glutamine can enhance the anticancer properties of 3-bromopyruvate, a halogenated analog of pyruvic acid. Glutamine deprival potentiated 3-bromopyruvate chemotherapy by increasing the stability of the monocarboxylate transporter-1, an effect that sensitized cells to metabolic oxidative stress and autophagic cell death. We further elucidated mechanisms through which resistance to chemopotentiation by glutamine deprival could be circumvented. Overall, our findings offer a preclinical proof-of-concept for how to employ 3-bromopyruvate or other monocarboxylic-based drugs to sensitize tumors to chemotherapy. PMID:22773663

  15. The relationship of individual and neighbourhood deprivation with morbidity in older adults: an observational study.

    PubMed

    Jordan, Kelvin P; Hayward, Richard; Roberts, Eyitope; Edwards, John J; Kadam, Umesh T

    2014-06-01

    The objective was to determine the relative association of social class and neighbourhood deprivation with primary care consultation for eight morbidities. In 18,047 survey responders aged ≥50 years, living in more deprived neighbourhoods was independently associated with new consultation for chronic obstructive pulmonary disease, ischaemic heart disease, diabetes, asthma and depression. Lower social class was associated with diabetes and chronic obstructive pulmonary disease. No such associations were found with otitis media, osteoarthritis or upper respiratory tract infection. These findings suggest a role of social environment in certain morbidities and indicate the importance of identifying and acting on neighbourhood deprivation to reduce health inequalities. PMID:24148556

  16. AKT-p53 axis protect cancer cells from autophagic cell death during nutrition deprivation.

    PubMed

    Sudhagar, S; Sathya, S; Gokulapriya, G; Lakshmi, B S

    2016-03-18

    An altered metabolism supports growth of tumor. AKT, a major signal integrator plays a key role in cell metabolism. We have shown that nutritional deprivation activates AKT as observed by increased phosphorylation of both Thr308 and Ser473. Pharmacological inhibition or silencing of AKT by siRNA affects cell viability during starvation. The tumor suppressor, p53 is also observed to be elevated during nutritional deprivation due to AKT. Silencing of AKT and p53 enhanced autophagy as evidenced by increased acidic vesicular organelles and LC3B II levels, suggesting AKT-p53 to play a significant role in cell survival through regulating autophagy during nutritional deprivation. PMID:26903300

  17. Chronobiological Therapy for Mood Disorders.

    PubMed

    Dallaspezia, Sara; Suzuki, Masahiro; Benedetti, Francesco

    2015-12-01

    Chronobiological therapies for mood disorders include manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance and the controlled exposure to light and darkness. Their antidepressant efficacy can overcome drug resistance and targets the core depressive symptoms including suicide, thus making them treatment options to be tried either alone or as adjunctive treatments combined with common psychopharmacological interventions. The specific pattern of mood change observed with chronobiological therapies is characterized by rapid and sustained effects, when used among themselves or combined with drugs. Effects sizes are the same reported for the most effective psychiatric treatments, but side effects are usually marginal or absent. New treatment protocols are developed to adapt them in different clinical settings. This review deals with the general principles of clinical chronobiology and the latest findings in this rapidly developing field. PMID:26478195

  18. Phase II Study of Dutasteride for Recurrent Prostate Cancer During Androgen Deprivation Therapy

    PubMed Central

    Shah, Satyan K.; Trump, Donald L.; Sartor, Oliver; Tan, Wei; Wilding, Gregory E.; Mohler, James L.

    2010-01-01

    Purpose We determined the response rate to and safety of a dual 5α-reductase inhibitor, dutasteride, in men with castration recurrent prostate cancer. Materials and Methods A total of 28 men with asymptomatic castration recurrent prostate cancer were treated with 3.5 mg dutasteride daily (luteinizing hormone-releasing hormone treatment continued), and evaluated monthly for response and toxicity. Eligibility included appropriate duration antiandrogen withdrawal, baseline prostate specific antigen 2.0 ng/ml or greater and a new lesion on bone scan, increase in measurable disease using Response Evaluation Criteria in Solid Tumors criteria, or 2 or more consecutive prostate specific antigen measurements increased over baseline. Outcomes were progression, stable disease, partial response (prostate specific antigen less than 50% of enrollment for 4 or more weeks) or complete response. Results There were 25 evaluable men with a mean age of 70 years (range 57 to 88), a mean prostate specific antigen of 61.9 ng/ml (range 5.0 to 488.9) and mean Gleason score 8 (range 6 to 10), 15 of whom had bone metastases. Eight men had 10 grade 3 or higher adverse events using National Cancer Institute Common Terminology Criteria, all of which were judged to be unrelated to treatment. Of the 25 men 14 had disease progression by 2 months, 9 had stable (2.5, 3, 3, 4, 4, 5, 5, 8.5, 9 months) disease, 2 had a partial response and none had a complete response. Overall median time to progression was 1.87 months (range 1 to 10, 95% CI 1.15–3.91). Conclusions Dutasteride rarely produces biochemical responses in men with castration recurrent prostate cancer. However, further study is warranted given its favorable safety profile. PMID:19091347

  19. Leptin Signaling Is Required for Leucine Deprivation-enhanced Energy Expenditure*

    PubMed Central

    Zhang, Qian; Liu, Bin; Cheng, Ying; Meng, Qingshu; Xia, Tingting; Jiang, Lei; Chen, Shanghai; Liu, Yong; Guo, Feifan

    2014-01-01

    Leptin signaling in the hypothalamus is crucial in energy homeostasis. We have previously shown that dietary deprivation of the essential amino acid leucine in mice stimulates fat loss by increasing energy expenditure. The involvement of leptin signaling in this regulation, however, has not been reported. Here, we show that leucine deprivation promotes leptin signaling in mice maintained on an otherwise normal diet and restores leptin responses in mice maintained on a high fat diet, a regimen known to induce leptin resistance. In addition, we found that leucine deprivation stimulated energy expenditure, and fat loss was largely blocked in db/db mice homozygous for a mutation in leptin receptor and a knock-in mouse line Y3F with abrogation of leptin receptor Tyr1138-mediated signal transducer and activator transcript 3 signaling. Overall, our studies describe a novel link between hypothalamic leptin signaling and stimulation of energy expenditure under leucine deprivation. PMID:24302741

  20. Short-term feed deprivation alters immune status of surface mucosa in channel catfish (Ictalurus punctatus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Short-term feed deprivation (or fasting) is a common occurrence in aquacultured fish species whether due to season, production strategies, or disease. In channel catfish (Ictalurus punctatus) fasting impacts susceptibility to several bacterial pathogens including Flavobacterium columnare, the causat...

  1. Level of deprivation does not affect degree of discounting in pigeons

    PubMed Central

    Oliveira, Luís; Calvert, Amanda L.; Green, Leonard; Myerson, Joel

    2012-01-01

    Two experiments tested the effects of food deprivation on discounting in pigeons. An adjusting-amount procedure was used to estimate the subjective value of food at delays ranging from 1 to 24 s. Experiment 1 compared pigeons’ discounting of delayed food reinforcers at 75-80% and 90-95% of free-feeding weight. Experiment 2 compared discounting under 1-hr and 23-hr food deprivation. In both experiments at both deprivation levels, discounting was well described by the hyperboloid discounting function. No systematic effect of level of deprivation on degree of discounting was observed in either experiment. This finding is consistent with the view that pigeons’ choices are controlled by the relative, rather than the absolute, value of reinforcers. PMID:22983791

  2. Level of deprivation does not affect degree of discounting in pigeons.

    PubMed

    Oliveira, Luís; Calvert, Amanda L; Green, Leonard; Myerson, Joel

    2013-06-01

    Two experiments tested the effects of food deprivation on discounting in pigeons. An adjusting-amount procedure was used to estimate the subjective value of food at delays ranging from 1 to 24 s. Experiment 1 compared pigeons' discounting of delayed food reinforcers at 75 %-80 % and 90 %-95 % of free-feeding weight. Experiment 2 compared discounting under 1- and 23-h food deprivation. In both experiments at both deprivation levels, discounting was well described by the hyperboloid discounting function. No systematic effect of level of deprivation on degree of discounting was observed in either experiment. This finding is consistent with the view that pigeons' choices are controlled by the relative, rather than the absolute, value of reinforcers. PMID:22983791

  3. Sulbutiamine counteracts trophic factor deprivation induced apoptotic cell death in transformed retinal ganglion cells.

    PubMed

    Kang, Kui Dong; Majid, Aman Shah Abdul; Kim, Kyung-A; Kang, Kyungsu; Ahn, Hong Ryul; Nho, Chu Won; Jung, Sang Hoon

    2010-11-01

    Sulbutiamine is a highly lipid soluble synthetic analogue of vitamin B(1) and is used clinically for the treatment of asthenia. The aim of our study was to demonstrate whether sulbutiamine is able to attenuate trophic factor deprivation induced cell death to transformed retinal ganglion cells (RGC-5). Cells were subjected to serum deprivation for defined periods and sulbutiamine at different concentrations was added to the cultures. Various procedures (e.g. cell viability assays, apoptosis assay, reactive oxygen species analysis, Western blot analysis, flow cytometric analysis, glutathione (GSH) and glutathione-S-transferase (GST) measurement) were used to demonstrate the effect of sulbutiamine. Sulbutiamine dose-dependently attenuated apoptotic cell death induced by serum deprivation and stimulated GSH and GST activity. Moreover, sulbutiamine decreased the expression of cleaved caspase-3 and AIF. This study demonstrates for the first time that sulbutiamine is able to attenuate trophic factor deprivation induced apoptotic cell death in neuronal cells in culture. PMID:20809085

  4. Caffeine and REM sleep deprivation: Effect on basal levels of signaling molecules in area CA1.

    PubMed

    Alkadhi, Karim A; Alhaider, Ibrahim A

    2016-03-01

    We have investigated the neuroprotective effect of chronic caffeine treatment on basal levels of memory-related signaling molecules in area CA1 of sleep-deprived rats. Animals in the caffeine groups were treated with caffeine in drinking water (0.3g/l) for four weeks before they were REM sleep-deprived for 24h in the Modified Multiple Platforms paradigm. Western blot analysis of basal protein levels of plasticity- and memory-related signaling molecules in hippocampal area CA1 showed significant down regulation of the basal levels of phosphorylated- and total-CaMKII, phosphorylated- and total-CREB as well as those of BDNF and CaMKIV in sleep deprived rats. All these changes were completely prevented in rats that chronically consumed caffeine. The present findings suggest an important neuroprotective property of caffeine in sleep deprivation. PMID:26767416

  5. Long-term sleep deprivation as a game. The wear and tear of wakefulness.

    PubMed

    Kamphuisen, H A; Kemp, B; Kramer, C G; Duijvestijn, J; Ras, L; Steens, J

    1992-01-01

    We report here the first sleep deprivation study done on a group of 5 healthy students (1 female, 4 males, 23-24 years of age) while playing a game (Triviant). In 2 persons an EEG was recorded for 6 consecutive 24 h periods with an ambulatory monitor from the baseline night until 72 h after deprivation. The baseline night showed normal hypnograms. The students were deprived of sleep for 65 h following the baseline night. Sleep deprivation was complete and resulted in bradyphrenia, loss of memory and contact with reality, ataxia, decrease in body temperature and loss of body weight. The main sign of recuperation was a strongly increased slow-wave sleep synchronization during the first recuperation period (day-time sleep) only. There were no signs of REM rebound. PMID:1320535

  6. Human Hippocampal Structure: A Novel Biomarker Predicting Mnemonic Vulnerability to, and Recovery from, Sleep Deprivation.

    PubMed

    Saletin, Jared M; Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Stark, Shauna; Stark, Craig E; Walker, Matthew P

    2016-02-24

    Sleep deprivation impairs the formation of new memories. However, marked interindividual variability exists in the degree to which sleep loss compromises learning, the mechanistic reasons for which are unclear. Furthermore, which physiological sleep processes restore learning ability following sleep deprivation are similarly unknown. Here, we demonstrate that the structural morphology of human hippocampal subfields represents one factor determining vulnerability (and conversely, resilience) to the impact of sleep deprivation on memory formation. Moreover, this same measure of brain morphology was further associated with the quality of nonrapid eye movement slow wave oscillations during recovery sleep, and by way of such activity, determined the success of memory restoration. Such findings provide a novel human biomarker of cognitive susceptibility to, and recovery from, sleep deprivation. Moreover, this metric may be of special predictive utility for professions in which memory function is paramount yet insufficient sleep is pervasive (e.g., aviation, military, and medicine). PMID:26911684

  7. Dendritic sprouting and compensatory synaptogenesis in an identified interneuron follow auditory deprivation in a cricket.

    PubMed Central

    Hoy, R R; Nolen, T G; Casaday, G C

    1985-01-01

    We examined the effect of chronic afferent deprivation on an identified interneuron (Int-1) in the auditory system of the Australian field cricket Teleogryllus oceanicus. In normal intact crickets, the auditory afferents from each ear terminate ipsilaterally onto a single Int-1. Each bilaterally paired Int-1 is excited by ultrasound stimulation of its ipsilateral ear but not by the contralateral ear. Unilateral removal of an ear early in postembryonic development deprives the developing Int-1 of ipsilateral auditory innervation. Consequently, the ipsilateral dendrites of the deprived interneuron sprout, grow aberrantly across the ganglionic midline, and terminate specifically in the intact auditory neuropile of the contralateral (unlesioned) side, where they form functional synapses with the contralateral afferents. This unusual compensatory dendritic sprouting restores auditory function to the neuron. Thus, it is demonstrated that the dendritic shape of an identified Int, as well as its synaptic connectivity, is altered as a consequence of chronic sensory deprivation. Images PMID:3865195

  8. Nicotine Deprivation Produces Deficits in Pain Perception that are Moderately Attenuated by Caffeine Consumption.

    PubMed

    Baiamonte, Brandon A; Stickley, Sarah C; Ford, Sarah J

    2016-01-01

    During withdrawal, nicotine users experience aversive withdrawal symptoms, such as increased nociceptive processing, which may be responsible for subsequent use. Smokers often consume more caffeine than non-smokers and the combined effects of these two psychoactive drugs result in an enhanced analgesic effect of nicotine. We examined the effects of caffeine (via coffee consumption) and nicotine withdrawal on pain perception in minimally deprived smokers and non-smokers. Pain threshold and pain tolerance were assessed using a radiant heat stimulus before and 30 minutes after caffeine consumption. Nicotine deprivation (2 hrs) produced increases in pain threshold and decreases in pain tolerance representative of hyperalgesia. When smokers are nicotine deprived, caffeine consumption diminished baseline elevations in pain threshold, but had no effect on pain tolerance. These data suggest that caffeine consumption can dampen deficits in sensory discrimination related to pain during nicotine deprivation by reducing pain threshold to levels representative of non-smoking controls. PMID:27120004

  9. Alteration of pituitary-adrenal dynamics induced by a water deprivation regimen

    NASA Technical Reports Server (NTRS)

    Sakellaris, P. C.; Vernikos-Danellis, J.

    1974-01-01

    Experiments are described which were designed to assess the degree of adaptation that occurs in rats chronically exposed to the stress of a water-deprivation regimen and to determine if that adaptation represents a normalization of the hypothalamic-pituitary-adrenal axis. There were no significant differences in mean corticosterone concentrations among control nondeprived rats 1, 4, and 8 weeks after the start of the experiment. The water-deprived rats, however, had significantly elevated plasma steroids 1 and 4 weeks after the onset of deprivation as compared to controls, but not after 8 weeks. Thus, there was a significant decrease in mean plasma corticosterone levels during water deprivation from 1 week to 8 weeks.

  10. Comparative reproductive and physiological responses of northern bobwhite and scaled quail to water deprivation

    USGS Publications Warehouse

    Giuliano, W.M.; Patino, R.; Lutz, R.S.

    1998-01-01

    We compared reproductive and physiological responses of captive female northern bobwhite (Colinus virginianus) and scaled quail (Callipepla squamata) under control and water deprivation conditions. Scaled quail required less food and water to reproduce successfully under control conditions than northern bobwhite. Additionally, in scaled quail, serum osmolality levels and kidney mass were unaffected by water deprivation, whereas in northern bobwhite, serum osmolality levels increased and kidney mass declined. This finding indicates that scaled quail may have osmoregulatory abilities superior to those of northern bobwhite. Under control conditions, northern bobwhite gained more body mass and produced more but smaller eggs than scaled quail. Under water deprivation conditions, northern bobwhite lost more body mass but had more laying bens with a higher rate of egg production than scaled quail. Our data suggest that northern bobwhite allocated more resources to reproduction than to body maintenance, while scaled quail apparently forego reproduction in favor of body maintenance during water deprivation conditions.

  11. Deprivation and Social Support in Mental Health of Welfare Recipients in Japan.

    PubMed

    Yoshizumi, Takahiro; Mizutani, Seiko; Yamada, Soshiro

    2016-04-01

    Although many Western studies examining the mental health of welfare recipients exist, Japanese welfare recipients have been overlooked. This study investigated mental health among welfare recipients in Japan and relations with a sense of deprivation of life's necessities and social support. Participants (n = 305) completed the General Health Questionnaire-12 (GHQ-12), Proportional Deprivation Index, and a social support scale. Participants' GHQ-12 scores exceeded those of the general public, as 54.9% scored above the cut-off, suggesting poorer mental health among welfare recipients than the general population. Proportional Deprivation Index and emotional support from relatives and friends were associated with GHQ-12 scores. These results suggest that while chronic deprivation is associated with poorer mental health among welfare recipients, receiving emotional support may help cope with distress and maintain mental health. PMID:27154369

  12. EFFECTS ON THE FETUS OF MATERNAL BENOMYL EXPOSURE IN THE PROTEIN-DEPRIVED RAT

    EPA Science Inventory

    The separate and combined effects of protein deprivation and benomyl ((methyl 1-butylcarbomoyl)2-benzimidazole carbamate) exposure were studied in the pregnant rat fed a diet containing 24% (control) or 8% (deficient) casein throughout gestation. Within each diet group, subgroups...

  13. Court holds that patient in intensive care unit was not deprived of her liberty.

    PubMed

    Griffith, Richard

    Richard Griffith, Senior Lecturer in Health Law at Swansea University, discusses the difficult issue of deprivation of liberty when somebody lacks the capacity to make decisions about their own treatment. PMID:26878412

  14. Effects of sleep deprivation with reference to military operations.

    PubMed

    Giam, G C

    1997-01-01

    This review discusses the need for sleep, effects of sleep deprivation on behaviour and performance in the military, and sleep management recommendations to optimise combat effectiveness. Most people, regardless of sex or race, prefer 7 to 8 hours of sleep each night. Sleeping during the day is less recuperative. Continuous sleep is more effective than multiple short naps-even when the total hours for naps is more. Ten to 20 minute naps are useful when continuous sleep is not possible. Sleep inertia is the 5 to 30 minute period of sluggishness after awakening and important military tasks should be avoided. Previously, continuous work episodes (CWEs) duration was restricted by limited night vision, unreliable equipment and reduced endurance of military personnel. With improved technology, CWEs are now restricted primarily by endurance which is affected by sleep deprivation. This was one of the experiences noted in recent conflicts (e.g. Desert Storm) by personnel in the air force, army and navy. Since there will be changes in operational requirements, several work-rest-sleep plans must be prepared. Sleeping the preferred 7 to 8 hours per 24 hours the week before an operation may help prepare for optimal performance. Personnel should be familiarised with conditions under which they may sleep. During combat, sleep management should ideally avoid situations where all personnel are exhausted at the same time. As sleep debt accumulates, a person's mood, motivation, attention, alertness, short-term memory, ability to complete routines, task performance (errors of omission more than errors of commission) and physical performance will become more negatively affected. Counter measures must then be taken (e.g. time for sleep or naps, changing routines or rotating jobs). Drugs like caffeine and amphetamine can help personnel stay awake. However, they may also keep them awake when they need to sleep- and on awakening, they could suffer from "hang-overs" and are less efficient

  15. Feedback Blunting: Total Sleep Deprivation Impairs Decision Making that Requires Updating Based on Feedback

    PubMed Central

    Whitney, Paul; Hinson, John M.; Jackson, Melinda L.; Van Dongen, Hans P.A.

    2015-01-01

    Study Objectives: To better understand the sometimes catastrophic effects of sleep loss on naturalistic decision making, we investigated effects of sleep deprivation on decision making in a reversal learning paradigm requiring acquisition and updating of information based on outcome feedback. Design: Subjects were randomized to a sleep deprivation or control condition, with performance testing at baseline, after 2 nights of total sleep deprivation (or rested control), and following 2 nights of recovery sleep. Subjects performed a decision task involving initial learning of go and no go response sets followed by unannounced reversal of contingencies, requiring use of outcome feedback for decisions. A working memory scanning task and psychomotor vigilance test were also administered. Setting: Six consecutive days and nights in a controlled laboratory environment with continuous behavioral monitoring. Subjects: Twenty-six subjects (22–40 y of age; 10 women). Interventions: Thirteen subjects were randomized to a 62-h total sleep deprivation condition; the others were controls. Results: Unlike controls, sleep deprived subjects had difficulty with initial learning of go and no go stimuli sets and had profound impairment adapting to reversal. Skin conductance responses to outcome feedback were diminished, indicating blunted affective reactions to feedback accompanying sleep deprivation. Working memory scanning performance was not significantly affected by sleep deprivation. And although sleep deprived subjects showed expected attentional lapses, these could not account for impairments in reversal learning decision making. Conclusions: Sleep deprivation is particularly problematic for decision making involving uncertainty and unexpected change. Blunted reactions to feedback while sleep deprived underlie failures to adapt to uncertainty and changing contingencies. Thus, an error may register, but with diminished effect because of reduced affective valence of the feedback

  16. Changes in protein profiles of guinea pig sclera during development of form deprivation myopia and recovery

    PubMed Central

    Zhou, Xiangtian; Ye, Juxiu; Willcox, Mark D.P.; Xie, Ruozhong; Jiang, Liqin; Lu, Runxia; Shi, Jianzhen; Bai, Yan

    2010-01-01

    Purpose To investigate changes in protein profiles of posterior sclera in guinea pigs during development of form deprivation myopia and recovery. Methods Three groups of guinea pigs (developing form deprivation myopia, recovering from the myopia and normal control) were evaluated for protein profiles of the posterior sclera using two-dimensional gel electrophoresis. Protein spots with a different intensity of at least threefold among the 3 groups were further identified with mass spectrometry. Key proteins associated with ocular growth (crystallins) were examined at mRNA levels using RT–PCR. Results Moderate myopia was induced at 7 weeks of monocular deprivation and then more gradually recovered toward the previous refractive status 4 days after re-exposure of the eye to normal visual conditions. The profile of all protein spots at the posterior sclera was similar for both the deprived and the recovery eyes but distinct between either of the 2 experimental eyes and the normal control eyes. Twenty-six and 33 protein spots were differentially expressed in the deprived and the recovery eyes, respectively, compared to the normal control eyes. In contrast, the number of proteins differentially expressed between the deprived and the recovery eyes was only 5. Among the different subtypes of crystallins, βB2-crystallin was down-regulated and βA4-crystallin was upregulated in the deprived eyes at both protein and mRNA levels compared to the normal control eyes. The trend of expression for βA3/A1-crystallin was also similar at both mRNA and protein levels for the deprived eyes. However, αA-crystallin mRNA in the recovery eyes was upregulated while αA-crystallin itself was down-regulated. A similar inconsistency in expression of βA3/A1-, βA4-, and βB2-crystallins between the protein and mRNA levels also occurred in the recovery eyes. Conclusions Proteomic analysis provides a useful survey of the number of proteins whose levels change during form deprivation myopia

  17. The physiological effects of monocular deprivation and their reversal in the monkey's visual cortex.

    PubMed Central

    Blakemore, C; Garey, L J; Vital-Durand, F

    1978-01-01

    1. 1127 single units were recorded during oblique penetrations in area 17 of one normal, three monocularly deprived and four reverse sutured monkeys. 2. In all animals most cells outside layer IV c were orientation-selective, and preferred orientation usually shifted from cell to cell in a regular progressive sequence. 3. The presence in layer IV c of non-oriented, monocularly driven units, organized in alternating right-eye and left-eye 'stripes' (LeVay, Hubel & Wiesel, 1975) was confirmed. 4. Early monocular deprivation (2--5 1/2 weeks) caused a strong shift of ocular dominance towards the non-deprived eye. However, even outside layer IV c, neural background and some isolated cells could still be driven from the deprived eye in regularly spaced, narrow columnar regions. In layer IV c the non-deprived eye's stripes were almost three times wider, on average, than the deprived. 5. Later monocular deprivation (11--16 months) had no detectable influence on layer IV c but seemed to cause a small shift in ocular dominance outside IV c. Deprivation for 6 1/4 months in an adult had no such effect. 6. After early reverse suturing (at 5 1/2 weeks) the originally deprived eye gained dominance over cells outside layer IV c just as complete as that originally exercised by the eye that was first non-deprived. 7. The later reverse suturing was delayed, the less effective was recapture by the originally deprived eye. Reversal at 8 weeks led to roughly equal numbers of cells being dominated by each eye; fewer cells became dominated by the newly open eye after reverse suturing at 9 weeks and most of them were non-oriented; reversal at 38 1/2 weeks had no effect. 8. Binocular cells, though rare in reverse sutured animals, always had very similar preferred orientations in the two eyes. The columnar sequences of preferred orientation were not interrupted at the borders of ocular dominance columns. 9. Even within layer IV c there was evidence for re-expansion of physiologically

  18. Classifying Vulnerability to Sleep Deprivation Using Baseline Measures of Psychomotor Vigilance

    PubMed Central

    Patanaik, Amiya; Kwoh, Chee Keong; Chua, Eric C.P.; Gooley, Joshua J.; Chee, Michael W.L.

    2015-01-01

    Objective: To identify measures derived from baseline psychomotor vigilance task (PVT) performance that can reliably predict vulnerability to sleep deprivation. Design: Subjects underwent total sleep deprivation and completed a 10-min PVT every 1–2 h in a controlled laboratory setting. Participants were categorized as vulnerable or resistant to sleep deprivation, based on a median split of lapses that occurred following sleep deprivation. Standard reaction time, drift diffusion model (DDM), and wavelet metrics were derived from PVT response times collected at baseline. A support vector machine model that incorporated maximum relevance and minimum redundancy feature selection and wrapper-based heuristics was used to classify subjects as vulnerable or resistant using rested data. Setting: Two academic sleep laboratories. Participants: Independent samples of 135 (69 women, age 18 to 25 y), and 45 (3 women, age 22 to 32 y) healthy adults. Measurements and Results: In both datasets, DDM measures, number of consecutive reaction times that differ by more than 250 ms, and two wavelet features were selected by the model as features predictive of vulnerability to sleep deprivation. Using the best set of features selected in each dataset, classification accuracy was 77% and 82% using fivefold stratified cross-validation, respectively. Conclusions: Despite differences in experimental conditions across studies, drift diffusion model parameters associated reliably with individual differences in performance during total sleep deprivation. These results demonstrate the utility of drift diffusion modeling of baseline performance in estimating vulnerability to psychomotor vigilance decline following sleep deprivation. Citation: Patanaik A, Kwoh CK, Chua EC, Gooley JJ, Chee MW. Classifying vulnerability to sleep deprivation using baseline measures of psychomotor vigilance. SLEEP 2015;38(5):723–734. PMID:25325482

  19. Sleep Deprivation and Time-on-Task Performance Decrement in the Rat Psychomotor Vigilance Task

    PubMed Central

    Oonk, Marcella; Davis, Christopher J.; Krueger, James M.; Wisor, Jonathan P.; Van Dongen, Hans P.A.

    2015-01-01

    Study Objectives: The rat psychomotor vigilance task (rPVT) was developed as a rodent analog of the human psychomotor vigilance task (hPVT). We examined whether rPVT performance displays time-on-task effects similar to those observed on the hPVT. Design: The rPVT requires rats to respond to a randomly presented light stimulus to obtain a water reward. Rats were water deprived for 22 h prior to each 30-min rPVT session to motivate performance. We analyzed rPVT performance over time on task and as a function of the response-stimulus interval, at baseline and after sleep deprivation. Setting: The study was conducted in an academic research vivarium. Participants: Male Long-Evans rats were trained to respond to a 0.5 sec stimulus light within 3 sec of stimulus onset. Complete data were available for n = 20 rats. Interventions: Rats performed the rPVT for 30 min at baseline and after 24 h total sleep deprivation by gentle handling. Measurements and Results: Compared to baseline, sleep deprived rats displayed increased performance lapses and premature responses, similar to hPVT lapses of attention and false starts. However, in contrast to hPVT performance, the time-on-task performance decrement was not significantly enhanced by sleep deprivation. Moreover, following sleep deprivation, rPVT response times were not consistently increased after short response-stimulus intervals. Conclusions: The rat psychomotor vigilance task manifests similarities to the human psychomotor vigilance task in global performance outcomes, but not in post-sleep deprivation effects of time on task and response-stimulus interval. Citation: Oonk M, Davis CJ, Krueger JM, Wisor JP, Van Dongen HPA. Sleep deprivation and time-on-task performance decrement in the rat psychomotor vigilance task. SLEEP 2015;38(3):445–451. PMID:25515099

  20. The Impact of Partial Sleep Deprivation on Moral Reasoning in Military Officers

    PubMed Central

    Olsen, Olav Kjellevold; Pallesen, Ståle; Eid, Jarle

    2010-01-01

    Study Objectives: The present study explores the impact of long-term partial sleep deprivation on the activation of moral justice schemas, which are suggested to play a prominent role in moral reasoning and the formation of moral judgments and behavior. Design: Participants judged 5 dilemmas in rested and partially sleep deprived condition, in a counterbalanced design. Setting: In classroom and field exercises at the Norwegian Naval Academy and the Norwegian Army Academy. Participants: Seventy-one Norwegian naval and army officer cadets. Measurements and Results: The results showed that the officers' ability to conduct mature and principally oriented moral reasoning was severely impaired during partial sleep deprivation compared to the rested state. At the same time, the officers became substantially more rules-oriented in the sleep deprived condition, while self-oriented moral reasoning did not change. Interaction effects showed that those officers who displayed high levels of mature moral reasoning (n = 24) in the rested condition, lost much of this capacity during sleep deprivation in favor of a strong increase in rules-oriented moral reasoning as well as self-orientation. Conversely, officers at low levels of mature moral reasoning in rested condition (n = 23) were unaffected by sleep deprivation. Conclusions: The present data show that long-term partial sleep deprivation has an impact on the activation of moral justice schemas, and consequently on the ability to make moral justice judgments. Citation: Olsen OK; Pallesen S; Eid J. The impact of partial sleep deprivation on moral reasoning in military officers. SLEEP 2010;33(8):1086-1090. PMID:20815191

  1. Neighborhood deprivation and maternal psychological distress during pregnancy: a multilevel analysis.

    PubMed

    Yang, Seungmi; Kestens, Yan; Dahhou, Mourad; Daniel, Mark; Kramer, Michael S

    2015-05-01

    Maternal psychosocial distress is conceptualized as an important factor underlying the association between neighborhood deprivation and pregnancy outcomes. However, empirical studies to examine effects of neighborhood deprivation on psychosocial distress during pregnancy are scant. Based on a large multicenter cohort of pregnant women in Montreal, we examined (1) the extent to which psychosocial distress is clustered at the neighborhood-level, (2) the extent to which the clustering is explained by neighborhood material or social deprivation, and (3) whether associations between neighborhood deprivation and psychosocial distress persist after accounting for neighborhood composition (individual-level characteristics) using multilevel analyses. For 5,218 women residing in 740 neighborhoods, a prenatal interview at 24-26 gestational weeks measured both general and pregnancy-related psychological distress using well-validated scales: perceived stress, social support, depressive symptoms, optimism, commitment to the pregnancy, pregnancy-related anxiety, and maternal locus-of-control. Neighborhood deprivation indices were linked to study participants by their residential postal code. Neighborhood-level clustering (intraclass correlation) ranged from 1 to 2 % for perceived stress (lowest), optimism, pregnancy-related anxiety, and commitment to pregnancy to 4-6 % for perceived social support, depressive symptoms, and maternal locus of control (highest). Neighborhood material deprivation explained far more of the clustering (23-75 %) than did social deprivation (no more than 4 %). Although both material and social deprivation were associated with psychological distress in unadjusted analyses, the associations disappeared after accounting for individual-level socioeconomic characteristics. Our results highlight the importance of accounting for individual-level socioeconomic characteristics in studies of potential neighborhood effects on maternal mental health. PMID:25398620

  2. Material versus social deprivation and health: a case study of an urban area.

    PubMed

    Testi, Angela; Ivaldi, Enrico

    2009-07-01

    Socioeconomic factors are one of the main determinants of health inequalities. However, which component of socioeconomic status affects health most and how that relationship should be measured remains an open question. The aim of this study was to compare material and social deprivation indexes in order to determine which better explains health inequalities within an urban area. Following a review of the literature on small area deprivation indexes, a case study of the Italian city Genoa is presented. The city of Genoa is split into 71 small areas [urbanistic units (UU)], each of which has about 9,500 inhabitants. For each small area, socioeconomic indicators were extracted from the 2001 Census, whereas health indicators were computed from the death registry for 2001-2003. Factorial analyses was used to choose the deprivation variables, which were utilised to create two distinct deprivation indexes referring to material and social deprivation, respectively. Both deprivation indexes are positively correlated with health status proxied by standardised mortality ratios (SMRs) under 65. The material index, however, correlates more highly with SMRs than the social index, and thus the material index is the more suitable measure to explain variations in premature mortality within an urban area. Moreover, the two indexes must be kept distinct. PMID:19018580

  3. Acute total sleep deprivation potentiates cocaine-induced hyperlocomotion in mice.

    PubMed

    Berro, L F; Santos, R; Hollais, A W; Wuo-Silva, R; Fukushiro, D F; Mári-Kawamoto, E; Costa, J M; Trombin, T F; Patti, C L; Grapiglia, S B; Tufik, S; Andersen, M L; Frussa-Filho, R

    2014-09-01

    Sleep deprivation is common place in modern society. Nowadays, people tend to self-impose less sleep in order to achieve professional or social goals. In the social context, late-night parties are frequently associated with higher availability of recreational drugs with abuse potential. Physiologically, all of these drugs induce an increase in dopamine release in the mesolimbic dopaminergic system, which leads to hyperlocomotion in rodents. Sleep deprivation also seems to play an important role in the events related to the neurotransmission of the dopaminergic system by potentiating its behavioral effects. In this scenario, the aim of the present study was to investigate the effects of total sleep deprivation (6h) on the acute cocaine-induced locomotor stimulation in male mice. Animals were sleep deprived or maintained in their home cages and subsequently treated with an acute i.p. injection of 15mg/kg cocaine or saline and observed in the open field. Total sleep deprivation for 6h potentiated the hyperlocomotion induced by acute cocaine administration. In addition, the cocaine sleep deprived group showed a decreased ratio central/total locomotion compared to the cocaine control group, which might be related to an increase in the impulsiveness of mice. Our data indicate that acute periods of sleep loss should be considered risk factors for cocaine abuse. PMID:25067829

  4. Effect of Sleep Deprivation on the Male Reproductive System in Rats.

    PubMed

    Choi, Ji Ho; Lee, Seung Hoon; Bae, Jae Hyun; Shim, Ji Sung; Park, Hong Seok; Kim, Young Sik; Shin, Chol

    2016-10-01

    There has been no study reporting on the influence of sleep deprivation on the male reproductive system including sperm quality. In this study, we hypothesized that sleep deprivation could lead to adverse effect on the male reproductive system. The rats were divided into three groups: 1) control (home-cage, n = 10); 2) SD4 (sleep deprivation for 4 days, n = 10); and 3) SD7 (sleep deprivation for 7 days, n = 10). Sleep deprivation was performed by a modified multiple platform method. Sperm quality (sperm motion parameters and counts), hormone levels (corticosterone and testosterone), and the histopathology of testis were evaluated and compared between the three groups. A statistically significant reduction (P = 0.018) was observed in sperm motility in the SD7 group compared to those of the control group. However, there were no significant differences in other sperm motion parameters, or in sperm counts of the testis and cauda epididymis between three groups. Compared with the control group, the SD4 (P = 0.033) and SD7 (P = 0.002) groups exhibited significant increases of corticosterone levels, but significant decreases of testosterone levels were found in the SD4 (P = 0.001) and SD7 (P < 0.001) groups. Seminiferous tubular atrophy and/or spermatid retention was partially observed in the SD4 and SD7 groups, compared with the normal histopathology of the control group. Sleep deprivation may have an adverse effect on the male reproductive system in rats. PMID:27550492

  5. Early deprivation and home basal cortisol levels: a study of internationally adopted children.

    PubMed

    Kertes, Darlene A; Gunnar, Megan R; Madsen, Nicole J; Long, Jeffrey D

    2008-01-01

    Animal studies reveal that early deprivation impairs regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis, potentially increasing vulnerability to stressors throughout life. To examine early deprivation effects on basal HPA axis activity in humans, basal cortisol levels were examined in 164 internationally adopted children who had experienced varying degrees of preadoption deprivation. Duration of institutional care, age at adoption, and parent ratings of preadoption neglect indexed a latent factor of Deprived Care. Adoption measures of height and weight standardized to World Health Organisation norms indexed a latent factor of Growth Delay that was viewed as another reflection of deprivation. Cortisol samples were collected 3.3-11.6 years postadoption (Md = 7.3 years) at home on 3 days approximately 30 min after wakeup and before bedtime. Both early a.m. levels and the decrease in cortisol across the day were examined. A structural equation model revealed that preadoption Deprived Care predicted Growth Delay at adoption and Growth Delay predicted higher morning cortisol levels and a larger diurnal cortisol decrease. PMID:18423090

  6. Deprivation and Recovery of Sleep in Succession Enhances Reflexive Motor Behavior

    PubMed Central

    Sprenger, Andreas; Weber, Frederik D.; Machner, Bjoern; Talamo, Silke; Scheffelmeier, Sabine; Bethke, Judith; Helmchen, Christoph; Gais, Steffen; Kimmig, Hubert; Born, Jan

    2015-01-01

    Sleep deprivation impairs inhibitory control over reflexive behavior, and this impairment is commonly assumed to dissipate after recovery sleep. Contrary to this belief, here we show that fast reflexive behaviors, when practiced during sleep deprivation, is consolidated across recovery sleep and, thereby, becomes preserved. As a model for the study of sleep effects on prefrontal cortex-mediated inhibitory control in humans, we examined reflexive saccadic eye movements (express saccades), as well as speeded 2-choice finger motor responses. Different groups of subjects were trained on a standard prosaccade gap paradigm before periods of nocturnal sleep and sleep deprivation. Saccade performance was retested in the next morning and again 24 h later. The rate of express saccades was not affected by sleep after training, but slightly increased after sleep deprivation. Surprisingly, this increase augmented even further after recovery sleep and was still present 4 weeks later. Additional experiments revealed that the short testing after sleep deprivation was sufficient to increase express saccades across recovery sleep. An increase in speeded responses across recovery sleep was likewise found for finger motor responses. Our findings indicate that recovery sleep can consolidate motor disinhibition for behaviors practiced during prior sleep deprivation, thereby persistently enhancing response automatization. PMID:26048955

  7. Caffeine deprivation state modulates coffee consumption but not attentional bias for caffeine-related stimuli.

    PubMed

    Stafford, L D; Yeomans, M R

    2005-11-01

    Previous research has shown that caffeine deprivation state can exert a strong influence on the ability of caffeine to reinforce behaviour. Recent work has also found evidence for an attentional bias in habitual caffeine users. It remains unclear whether deprivation state can influence attentional bias. Here we explored the relationship between caffeine deprivation, attentional bias to caffeine-related stimuli and subsequent caffeine reinforcement measured by consumption of coffee. In three experiments, participants (between-subjects: n=28; within-subjects: n=20, within-subjects: n=20) were preloaded with either caffeine (experiments 1 and 3 : 100 mg; experiment 2 : 150 mg) or placebo, and in experiments 1 and 2 they completed a novel attentional bias task involving pre-attentive word recognition, and in experiment 3 a dot-probe task. In experiments 2 and 3, this was followed by a test of coffee consumption. Greater recognition for caffeine-related words (experiments 1 and 2) and faster reaction times to probes replacing caffeine-related rather than control stimuli (experiment 3) confirmed caffeine-related attentional biases, but in no case was this affected by manipulation of caffeine-deprivation state. Participants in a deprived versus nondeprived state, however, experienced increases in drowsiness and headaches (experiment 2) and reduced alertness (experiment 3). Further, coffee consumption was greatest when participants were caffeine-deprived than when they were nondeprived. Findings are discussed in relation to prevailing theories of drug addiction. PMID:16170233

  8. A small polypeptide triggers complete degradation of light-harvesting phycobiliproteins in nutrient-deprived cyanobacteria.

    PubMed Central

    Collier, J L; Grossman, A R

    1994-01-01

    Phycobilisomes are the multiprotein complexes predominantly responsible for harvesting light energy in cyanobacteria and some eukaryotic algae. When the cyanobacterium Synechococcus sp. strain PCC 7942 is deprived of an essential nutrient, the phycobilisomes are specifically and rapidly degraded. Degradation may be either partial (after phosphorus deprivation) or complete (after sulfur or nitrogen deprivation). We have developed a visual screen to obtain mutants unable to degrade their phycobilisomes upon nutrient starvation. Complementation of one of these mutants led to the identification of a gene, designated nblA, that encodes a 59 amino acid polypeptide essential for phycobilisome degradation. Transcription of nblA increases dramatically in sulfur- or nitrogen-deprived cells and moderately in phosphorus-deprived cells. Using the phosphorus-regulated alkaline phosphatase (phoA) promoter as a tool, we engineered constructs from which we could control the expression of either sense or antisense nblA. Increased expression of sense nbLA caused complete phycobilisome degradation during phosphorus deprivation, while expression of antisense nblA prevented phycobilisome degradation. Hence, nblA is necessary, and may be sufficient, for the degradation of phycobilisomes under adverse environmental conditions. Further investigation of the mechanism by which nblA causes phycobilisome destruction may reveal general principles that govern the specificity of macromolecular complex degradation. Images PMID:8131738

  9. Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex

    PubMed Central

    Pourzia, Olivia; Feldman, Daniel E.

    2016-01-01

    Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1) during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation. PMID:26840956

  10. Tempol protects sleep-deprivation induced behavioral deficits in aggressive male Long-Evans rats.

    PubMed

    Solanki, Naimesh; Atrooz, Fatin; Asghar, Saman; Salim, Samina

    2016-01-26

    Earlier, we reported that elevated anxiety-like behavior and high aggression in aged retired breeder Long-Evans (L-E) rats was associated with increased plasma corticosterone and elevated oxidative stress levels. In the present study, we examined how this aged aggressive and anxious rat strain responds to acute sleep deprivation (24h) and whether their behaviors can be modulated via antioxidant tempol treatment. Four groups of L-E rats were utilized: naïve control (NC), tempol treated control (T+NC), sleep deprived (SD), tempol treated and sleep deprived (T+SD). Thus, two groups were treated with tempol (1mM in drinking water for 2 weeks) while the other two were not. Two groups were subjected to acute sleep deprivation (24h) using the columns-in-water model while the other two were not. Sleep deprivation induced anxiety-like behavior, led to significant depression-like behavior and short-term memory impairment in SD rats. And, decision-making behavior also was compromised in SD rats. These behavioral and cognitive impairments were prevented with tempol treatment in T+SD rats. Tempol treatment also reduced SD-induced increase in corticosterone and oxidative stress levels in T+SD rats. These results suggest potential involvement of oxidative stress mechanisms in regulation of sleep deprivation induced behavioral and cognitive deficits in male aged-aggressive rats. PMID:26724222

  11. A PILOT STUDY ON THE ENCODING OF A PERCEPTUAL LEARNING TASK FOLLOWING SLEEP DEPRIVATION.

    PubMed

    McWhirter, Kelly K; Morrow, Anne S; Lee, Beth A; Bishu, Shrinivas; Zametkin, Alan J; Balkin, Thomas J; Smith, Carolyn B; Picchioni, Dante

    2015-08-01

    Memory encoding sometimes must occur during a period of sleep deprivation. The question was whether one night of sleep deprivation inhibits encoding on a perceptual learning task (the texture discrimination task). The sample was 18 human participants (M age=22.1 yr., SEM=0.5; 8 men). The participants were randomized to a sleep deprivation or sleep control condition and, after the manipulation, were given two administrations of the texture discrimination task. All participants were given an opportunity for a 90 min. nap between the two administrations. Performance was measured by the interpolated stimulus-to-mask-onset asynchrony (i.e., the inter-stimulus interval), at which the percentage of correct responses for the stimuli in the participant's peripheral vision fell below 80%. Offline consolidation was defined as a decrease in this index between the two administrations. Participants who were sleep deprived prior to encoding exhibited similar offline consolidation (M=-5.3 msec., SEM=2.3) compared to participants who were not sleep deprived prior to encoding (M=-6.2 msec., SEM=3.9); the two-way interaction between time and condition was not significant. In light of reports in the literature, these results indicate encoding following sleep deprivation may be influenced by both the type of task encoded and the brain regions involved in memory processing. PMID:26226287

  12. Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis.

    PubMed

    Tudor, Jennifer C; Davis, Emily J; Peixoto, Lucia; Wimmer, Mathieu E; van Tilborg, Erik; Park, Alan J; Poplawski, Shane G; Chung, Caroline W; Havekes, Robbert; Huang, Jiayan; Gatti, Evelina; Pierre, Philippe; Abel, Ted

    2016-01-01

    Sleep deprivation is a public health epidemic that causes wide-ranging deleterious consequences, including impaired memory and cognition. Protein synthesis in hippocampal neurons promotes memory and cognition. The kinase complex mammalian target of rapamycin complex 1 (mTORC1) stimulates protein synthesis by phosphorylating and inhibiting the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2). We investigated the involvement of the mTORC1-4EBP2 axis in the molecular mechanisms mediating the cognitive deficits caused by sleep deprivation in mice. Using an in vivo protein translation assay, we found that loss of sleep impaired protein synthesis in the hippocampus. Five hours of sleep loss attenuated both mTORC1-mediated phosphorylation of 4EBP2 and the interaction between eukaryotic initiation factor 4E (eIF4E) and eIF4G in the hippocampi of sleep-deprived mice. Increasing the abundance of 4EBP2 in hippocampal excitatory neurons before sleep deprivation increased the abundance of phosphorylated 4EBP2, restored the amount of eIF4E-eIF4G interaction and hippocampal protein synthesis to that seen in mice that were not sleep-deprived, and prevented the hippocampus-dependent memory deficits associated with sleep loss. These findings collectively demonstrate that 4EBP2-regulated protein synthesis is a critical mediator of the memory deficits caused by sleep deprivation. PMID:27117251

  13. Psychotic-Like Experiences and Their Cognitive Appraisal Under Short-Term Sensory Deprivation

    PubMed Central

    Daniel, Christina; Lovatt, Anna; Mason, Oliver John

    2014-01-01

    Aims: This study aimed to establish and compare the effects of brief sensory deprivation on individuals differing in trait hallucination proneness. Method: Eighteen participants selected for high hallucination proneness were compared against 18 participants rating low on this trait. The presence of psychotic-like experiences (PLEs), and participants’ cognitive appraisals of these, was evaluated in three different settings: at baseline, in a “secluded office” environment, and in light-and-sound sensory deprivation. Results: Psychotic-like experiences were experienced significantly more often in sensory deprivation for both groups. In particular, both experienced slight increases in perceptual distortions and anhedonia in seclusion, and these increased further during sensory deprivation. Highly hallucination prone individuals showed a significantly greater increase in perceptual distortions in sensory deprivation than did non-prone individuals suggesting a state-trait interaction. Their appraisals of these anomalous experiences were compared to both clinical and non-clinical individuals experiencing psychotic symptoms in everyday life. Conclusion: Short-term sensory deprivation is a potentially useful paradigm to model psychotic experiences, as it is a non-pharmacological tool for temporarily inducing psychotic-like states and is entirely safe at short duration. Experiences occur more frequently, though not exclusively, in those at putative risk of a psychotic disorder. The appraisals of anomalous experiences arising are largely consistent with previous observations of non-clinical individuals though importantly lacked the general positivity of the latter. PMID:25177302

  14. Neurobehavioral and Cognitive Changes Induced by Sleep Deprivation in Healthy Volunteers.

    PubMed

    Cassé-Perrot, Catherine; Lanteaume, Laura; Deguil, Julie; Bordet, Régis; Auffret, Alexandra; Otten, Lisa; Blin, Olivier; Bartrés-Faz, David; Micallef, Joëlle

    2016-01-01

    To this day, the pharmacological treatment of Alzheimer's disease remains limited to the temporary stabilisation of cognitive decline and the reduction of neuropsychiatric symptoms. It is moreover with great difficulty to predict and select promising drug candidates in the early stages of the discovery and developmental process. In this context, scientists have developed new experimental paradigms to artificially induce transient cognitive impairments in healthy volunteers akin to those observed in Alzheimer's disease, i.e. the Cognitive Challenge Models. In the last decade, a great amount of literature on Sleep Deprivation was published which mainly focused on the consequences of sleep loss for public health. However, sleep deprivation paradigm may also be regarded as a cognitive challenge model. It is commonly accepted that sleep deprivation induces cognitive impairments related to a global decrease in vigilance, while in fact, there is a controversial approach related to the selective effects on cognitive functions. The identification and validation of cognitive challenge models in healthy volunteers are suitable in early clinical development of drugs to determine the 'hint of efficacy' of drug candidates. The present review aims at exploring in detail the methods, designs and cognitive paradigms used in non pharmacological sleep deprivation studies. Sleep deprivation can be induced by different methods. Probing the four main cognitive functions will allow identifying the extent to which different sleep deprivation designs selectively compromise executive function, working memory, episodic memory and attention. Findings will be discussed in line with cognitive processing levels that are required according to the tasks. PMID:27189463

  15. Does food vendor density mediate the association between neighborhood deprivation and BMI? A G-computation mediation analysis

    PubMed Central

    Zhang, Y. Tara; Laraia, Barbara A.; Mujahid, Mahasin S.; Tamayo, Aracely; Blanchard, Samuel D.; Warton, E. Margaret; Kelly, N. Maggi; Moffet, Howard H.; Schillinger, Dean; Adler, Nancy; Karter, Andrew J.

    2015-01-01

    Background In previous research, neighborhood deprivation was positively associated with body mass index (BMI) among adults with diabetes. We assessed whether the association between neighborhood deprivation and BMI is attributable, in part, to geographic variation in the availability of healthful and unhealthful food vendors. Methods Subjects were 16,634 participants of the Diabetes Study of Northern California (DISTANCE), a multiethnic cohort of adults living with diabetes. Neighborhood deprivation and healthful (supermarket and produce) and unhealthful (fast food outlets and convenience stores) food vendor kernel density were calculated at each participant's residential block centroid. We estimated the total effect, controlled direct effect, natural direct effect, and natural indirect effect of neighborhood deprivation on BMI. Mediation effects were estimated using G-computation, a maximum likelihood substitution estimator of the G-formula that allows for complex data relationships such as multiple mediators and sequential causal pathways. Results We estimated that if neighborhood deprivation were reduced from the most deprived to the least deprived quartile, average BMI would change by −0.73 units (95% CI −1.05, −0.32); however, we did not detect evidence of mediation by food vendor density. In contrast to previous findings, a simulated reduction in neighborhood deprivation from the most deprived to the least deprived quartile was associated with dramatic declines in both healthful and unhealthful food vendor density. PMID:25741628

  16. Social deprivation affects cooperative predator inspection in a cichlid fish

    PubMed Central

    Hesse, Saskia; Anaya-Rojas, Jaime M.; Frommen, Joachim G.; Thünken, Timo

    2015-01-01

    The social environment individuals are exposed to during ontogeny shapes social skills and social competence in group-living animals. Consequently, social deprivation has serious effects on behaviour and development in animals but little is known about its impact on cooperation. In this study, we examined the effect of social environment on cooperative predator inspection. Predator inspection behaviour is a complex behaviour, which is present in a variety of shoaling fish species. Often, two fish leave the safety of the group and inspect a potentially dangerous predator in order to gather information about the current predation risk. As predator inspection is highly risky, it is prone to conflicts and cheating. However, cooperation among individuals may reduce the individual predation risk. We investigated this complex social behaviour in juveniles of the cichlid fish Pelvicachromis taeniatus that were reared in two different social environments throughout development. Fish reared in a group inspected more often than isolation-reared fish and were more likely to cooperate, i.e. they conducted conjoint inspection of a predator. By contrast, isolation-reared fish were more likely to perform a single inspection without a companion. These results suggest an impairment of cooperative behaviour in isolation-reared fish most probably due to lack of social experience and resulting in lowered social skills needed in coordinated behaviour. PMID:26064616

  17. Changes to coral health and metabolic activity under oxygen deprivation.

    PubMed

    Murphy, James W A; Richmond, Robert H

    2016-01-01

    On Hawaiian reefs, the fast-growing, invasive algae Gracilaria salicornia overgrows coral heads, restricting water flow and light, thereby smothering corals. Field data shows hypoxic conditions (dissolved oxygen (DO2) < 2 mg/L) occurring underneath algal mats at night, and concurrent bleaching and partial tissue loss of shaded corals. To analyze the impact of nighttime oxygen-deprivation on coral health, this study evaluated changes in coral metabolism through the exposure of corals to chronic hypoxic conditions and subsequent analyses of lactate, octopine, alanopine, and strombine dehydrogenase activities, critical enzymes employed through anaerobic respiration. Following treatments, lactate and octopine dehydrogenase activities were found to have no significant response in activities with treatment and time. However, corals subjected to chronic nighttime hypoxia were found to exhibit significant increases in alanopine dehydrogenase activity after three days of exposure and strombine dehydrogenase activity starting after one overnight exposure cycle. These findings provide new insights into coral metabolic shifts in extremely low-oxygen environments and point to ADH and SDH assays as tools for quantifying the impact of hypoxia on coral health. PMID:27114888

  18. Changes to coral health and metabolic activity under oxygen deprivation

    PubMed Central

    Richmond, Robert H.

    2016-01-01

    On Hawaiian reefs, the fast-growing, invasive algae Gracilaria salicornia overgrows coral heads, restricting water flow and light, thereby smothering corals. Field data shows hypoxic conditions (dissolved oxygen (DO2) < 2 mg/L) occurring underneath algal mats at night, and concurrent bleaching and partial tissue loss of shaded corals. To analyze the impact of nighttime oxygen-deprivation on coral health, this study evaluated changes in coral metabolism through the exposure of corals to chronic hypoxic conditions and subsequent analyses of lactate, octopine, alanopine, and strombine dehydrogenase activities, critical enzymes employed through anaerobic respiration. Following treatments, lactate and octopine dehydrogenase activities were found to have no significant response in activities with treatment and time. However, corals subjected to chronic nighttime hypoxia were found to exhibit significant increases in alanopine dehydrogenase activity after three days of exposure and strombine dehydrogenase activity starting after one overnight exposure cycle. These findings provide new insights into coral metabolic shifts in extremely low-oxygen environments and point to ADH and SDH assays as tools for quantifying the impact of hypoxia on coral health. PMID:27114888

  19. Early growth response 1 regulates glucose deprivation-induced necrosis

    PubMed Central

    JEON, HYUN MIN; LEE, SU YEON; JU, MIN KYUNG; KIM, CHO HEE; PARK, HYE GYEONG; KANG, HO SUNG

    2013-01-01

    Necrosis is commonly found in the core region of solid tumours due to metabolic stress such as hypoxia and glucose deprivation (GD) resulting from insufficient vascularization. Necrosis promotes tumour growth and development by releasing the tumour-promoting cytokine high mobility group box 1 (HMGB1); however, the molecular mechanism underlying necrotic cell death remains largely unknown. In this study, we show that early growth response 1 (Egr-1) is induced in a reactive oxygen species (ROS)-dependent manner by GD in several cell lines such as A549, MDA-MB-231 and HepG2 cells that exhibit necrosis upon GD. We found that Egr-1 short hairpin RNA (shRNA) prevented GD-induced necrosis and HMGB1 release. Necrosis-inhibiting activity of Egr-1 shRNA was also seen in multicellular tumour spheroids (MTSs), an in vitro tumour model system. In contrast, Egr-1 overexpression appeared to make tumour cells more susceptible to GD-induced necrosis. Finally, Egr-1 shRNA suppressed the growth of MTSs. These findings demonstrate that Egr-1 is implicated in GD-induced necrosis and tumour progression. PMID:23152075

  20. Chlamydomonas Flavodiiron Proteins Facilitate Acclimation to Anoxia During Sulfur Deprivation

    PubMed Central

    Jokel, Martina; Kosourov, Sergey; Battchikova, Natalia; Tsygankov, Anatoly A.; Aro, Eva Mari; Allahverdiyeva, Yagut

    2015-01-01

    The flavodiiron proteins (FDPs) are involved in the detoxification of oxidative compounds, such as nitric oxide (NO) or O2 in Archaea and Bacteria. In cyanobacteria, the FDPs Flv1 and Flv3 are essential in the light-dependent reduction of O2 downstream of PSI. Phylogenetic analysis revealed that two genes (flvA and flvB) in the genome of Chlamydomonas reinhardtii show high homology to flv1 and flv3 genes of the cyanobacterium Synechocystis sp. PCC 6803. The physiological role of these FDPs in eukaryotic green algae is not known, but it is of a special interest since these phototrophic organisms perform oxygenic photosynthesis similar to higher plants, which do not possess FDP homologs. We have analyzed the levels of flvA and flvB transcripts in C. reinhardtii cells under various environmental conditions and showed that these genes are highly expressed under ambient CO2 levels and during the early phase of acclimation to sulfur deprivation, just before the onset of anaerobiosis and the induction of efficient H2 photoproduction. Importantly, the increase in transcript levels of the flvA and flvB genes was also corroborated by protein levels. These results strongly suggest the involvement of FLVA and FLVB proteins in alternative electron transport. PMID:26063391

  1. The Nature of Consciousness in the Visually Deprived Brain

    PubMed Central

    Kupers, Ron; Pietrini, Pietro; Ricciardi, Emiliano; Ptito, Maurice

    2011-01-01

    Vision plays a central role in how we represent and interact with the world around us. The primacy of vision is structurally imbedded in cortical organization as about one-third of the cortical surface in primates is involved in visual processes. Consequently, the loss of vision, either at birth or later in life, affects brain organization and the way the world is perceived and acted upon. In this paper, we address a number of issues on the nature of consciousness in people deprived of vision. Do brains from sighted and blind individuals differ, and how? How does the brain of someone who has never had any visual perception form an image of the external world? What is the subjective correlate of activity in the visual cortex of a subject who has never seen in life? More in general, what can we learn about the functional development of the human brain in physiological conditions by studying blindness? We discuss findings from animal research as well from recent psychophysical and functional brain imaging studies in sighted and blind individuals that shed some new light on the answers to these questions. PMID:21713178

  2. Is sleep deprivation a contributor to obesity in children?

    PubMed

    Chaput, Jean-Philippe

    2016-03-01

    Chronic lack of sleep (called "sleep deprivation") is common in modern societies with 24/7 availability of commodities. Accumulating evidence supports the role of reduced sleep as contributing to the current obesity epidemic in children and youth. Longitudinal studies have consistently shown that short sleep duration is associated with weight gain and the development of obesity. Recent experimental studies have reported that sleep restriction leads to weight gain in humans. Increased food intake appears to be the main mechanism by which insufficient sleep results in weight gain. Voluntary sleep restriction has been shown to increase snacking, the number of meals eaten per day, and the preference for energy-dense foods. Although the causes of sleep loss in the pediatric population are numerous, more research looking at screen exposure before bedtime and its effects on sleep is needed given the pervasiveness of electronic media devices in today's environment. Health professionals should routinely ask questions about sleep and promote a good night's sleep because insufficient sleep impacts activity and eating behaviors. Future research should examine the clinical benefits of increasing sleep duration on eating behaviors and body weight control and determine the importance of adequate sleep to improve the treatment of obesity. PMID:26576804

  3. Chlamydomonas Flavodiiron Proteins Facilitate Acclimation to Anoxia During Sulfur Deprivation.

    PubMed

    Jokel, Martina; Kosourov, Sergey; Battchikova, Natalia; Tsygankov, Anatoly A; Aro, Eva Mari; Allahverdiyeva, Yagut

    2015-08-01

    The flavodiiron proteins (FDPs) are involved in the detoxification of oxidative compounds, such as nitric oxide (NO) or O(2) in Archaea and Bacteria. In cyanobacteria, the FDPs Flv1 and Flv3 are essential in the light-dependent reduction of O(2) downstream of PSI. Phylogenetic analysis revealed that two genes (flvA and flvB) in the genome of Chlamydomonas reinhardtii show high homology to flv1 and flv3 genes of the cyanobacterium Synechocystis sp. PCC 6803. The physiological role of these FDPs in eukaryotic green algae is not known, but it is of a special interest since these phototrophic organisms perform oxygenic photosynthesis similar to higher plants, which do not possess FDP homologs. We have analyzed the levels of flvA and flvB transcripts in C. reinhardtii cells under various environmental conditions and showed that these genes are highly expressed under ambient CO(2) levels and during the early phase of acclimation to sulfur deprivation, just before the onset of anaerobiosis and the induction of efficient H(2) photoproduction. Importantly, the increase in transcript levels of the flvA and flvB genes was also corroborated by protein levels. These results strongly suggest the involvement of FLVA and FLVB proteins in alternative electron transport. PMID:26063391

  4. Proteomics of phosphate use and deprivation in plants.

    PubMed

    Alexova, Ralitza; Millar, A Harvey

    2013-02-01

    Phosphate is an essential element for plants and is involved in the composition of sugar phosphates, nucleic acids, membrane lipids, and energy metabolism via the generation of ATP. Crop farming requires the application of large amounts of phosphate fertilizer, but the fossilized rock deposits used as a commercial source of phosphate fertilizer are a nonrenewable resource that is predicted to reach a peak within the next century and drive plant production costs up as the global demand for food increases. Recent progress in the identification of key molecular regulators of the plant response to phosphate deprivation has highlighted differences in the response of the model plant Arabidopsis compared to economically important crops. This review focuses on the potential of proteomics to unravel the common and specific biochemical changes that contribute to phosphate use efficiency in cultivars of rice, maize, and oilseed rape. Proteome studies reveal a wide scope of species-specific metabolic strategies that lead to changes in root morphology and metabolism, driven by secretion of specific proteins and alteration of energy metabolism, carbon, and nitrogen assimilation inside the root cells. Understanding of the mechanisms underlying plant phosphate use efficiency in crops is critical for developing sustainable agriculture practices. PMID:23281194

  5. Altered representation of facial expressions after early visual deprivation

    PubMed Central

    Gao, Xiaoqing; Maurer, Daphne; Nishimura, Mayu

    2013-01-01

    We investigated the effects of early visual deprivation on the underlying representation of the six basic emotions. Using multi-dimensional scaling (MDS), we compared the similarity judgments of adults who had missed early visual input because of bilateral congenital cataracts to control adults with normal vision. Participants made similarity judgments of the six basic emotional expressions, plus neutral, at three different intensities. Consistent with previous studies, the similarity judgments of typical adults could be modeled with four underlying dimensions, which can be interpreted as representing pleasure, arousal, potency and intensity of expressions. As a group, cataract-reversal patients showed a systematic structure with dimensions representing pleasure, potency, and intensity. However, an arousal dimension was not obvious in the patient group's judgments. Hierarchical clustering analysis revealed a pattern in patients seen in typical 7-year-olds but not typical 14-year-olds or adults. There was also more variability among the patients than among the controls, as evidenced by higher stress values for the MDS fit to the patients' data and more dispersed weightings on the four dimensions. The findings suggest an important role for early visual experience in shaping the later development of the representations of emotions. Since the normal underlying structure for emotion emerges postnatally and continues to be refined until late childhood, the altered representation of emotion in adult patients suggests a sleeper effect. PMID:24312071

  6. Selenium deficiency induced by zinc deprivation in a crustacean

    SciTech Connect

    Keating, K.I.; Caffrey, P.B. )

    1989-08-01

    For intact daphnids reared in circumstances of controlled trace element exposure, one consequence of insufficient zinc (Zn) is an increased demand on the animal's pool of available selenium (Se). This demand is manifested by the type of cuticle deterioration associated with Se deficiency and by a depression of reproduction. In the presence of 25 parts per billion (ppb) Zn, 1 ppb Se eliminates these symptoms. In the absence of detectable Zn, 5 ppb Se eliminates overt cuticle damage and substantially increases reproduction. A shortening of life span resulting from Zn deprivation is not ameliorated by Se addition. The authors suggest that the interplay between Zn and Se concentrations reflects an underlying interplay between interdependent, but distinct, metabolic pathways; i.e., (for Se) glutathione peroxidase and (for Zn) Cu,Zn-superoxide dismutase--each offering protection against free radical damage. Because they are not necessarily localized in a given tissue, the key to recognition of such subtle, complex trace nutrient interactions has been use of intact animals in circumstances of control previously attainable only in tissue cultures.

  7. Sleep Deprivation Aggravates Median Nerve Injury-Induced Neuropathic Pain and Enhances Microglial Activation by Suppressing Melatonin Secretion

    PubMed Central

    Huang, Chun-Ta; Chiang, Rayleigh Ping-Ying; Chen, Chih-Li; Tsai, Yi-Ju

    2014-01-01

    Study Objectives: Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects. Design: Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day. Participants: Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used. Measurements: Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines. Results: In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines. Conclusions: Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity. Citation: Huang CT, Chiang RP, Chen CL, Tsai YJ. Sleep

  8. 'First, do no harm': managing the metabolic impacts of androgen deprivation in men with advanced prostate cancer.

    PubMed

    Lomax, A J; Parente, P; Gilfillan, C; Livingston, P M; Davis, I D; Pezaro, C

    2016-02-01

    Androgen deprivation therapy (ADT) is a standard systemic treatment for men with prostate cancer. Men on ADT may be elderly and have comorbidities that are exacerbated by ADT, such as cardiovascular disease, diabetes, obesity, sedentary lifestyle and osteoporosis. Studies on managing the impacts of ADT have focused on men with non-metastatic disease, where ADT is given for a limited duration. However, some men with advanced or metastatic prostate cancer will achieve long-term survival with palliative ADT and therefore also risk morbidity from prolonged ADT. Furthermore, ADT is continued during the use of other survival-prolonging therapies for men with advanced disease, and there is a general trend to use ADT earlier in the disease course. As survival improves, management of the metabolic effects of ADT becomes important for maintaining both quality and quantity of life. This review will outline the current data, offer perspectives for management of ADT complications in men with advanced prostate cancer and discuss avenues for further research. PMID:25732203

  9. Sleep deprivation worsens inflammation and delays recovery in a mouse model of colitis

    PubMed Central

    Tang, Yueming; Preuss, Fabian; Turek, Fred W.; Jakate, Shriram; Keshavarzian, Ali

    2012-01-01

    Background and aim We recently showed that patients with inflammatory bowel disease (IBD) report significantly more sleep disturbances. To determine whether disrupted sleep can affect the severity of inflammation and the course of IBD, we used an animal model of colonic inflammation to determine the effects of acute and chronic intermittent sleep deprivation on the severity of colonic inflammation and tissue damage in colitis and recovery from this damage. Methods Acute sleep deprivation (ASD) consisted of 24 h of forced locomotor activity in a mechanical wheel rotating at a constant speed. Chronic intermittent sleep deprivation (CISD) consisted of an acute sleep deprivation episode, followed by additional sleep deprivation periods in the wheel for 6 h every other day throughout the 10 day study period. To induce colitis, mice were given 2% dextran sodium sulfate (DSS) in their daily drinking water for 7 days. The development and severity of colitis were monitored by measuring weight loss and tissue myeloperoxidase (MPO) activity daily and colon histology scores 10 days after initiation of colitis. Results ASD or CISD did not cause colonic inflammation in vehicle-treated mice. Changes in daily body weight, tissue MPO levels and colon histopathology score were similar between mice that were sleep deprived and controls. Daily DSS ingestion caused colitis in mice. ASD worsened colonic inflammation: tissue MPO levels in ASD/DSS-treated mice were significantly higher than in DSS-treated mice that were not sleep deprived. However, the worsening of colonic inflammation by ASD was not enough to exacerbate clinical manifestations of colitis such as weight loss. In contrast, the deleterious effects of CISD were severe enough to cause worsening of histological and clinical manifestations of colitis. The deleterious effects of sleep deprivation on severity of colitis appeared to be due to both increased colonic inflammation and a decrease in the ability of mice to recover from

  10. Deprivation of Liberty: Collected Guidance Various authors Deprivation of Liberty: Collected Guidance 400pp £29.95 Law Society Publishing 9781784460433 1784460435 [Formula: see text].

    PubMed

    2016-08-31

    Deprivation of liberty is a complicated and confusing subject, which can be challenging for healthcare professionals. Understanding and applying its safeguards can be difficult because of the complex set of regulations, as well as various sources of guidance, and it can be a challenge to find practical information that will help. PMID:27577305

  11. Implementation of High-Dose-Rate Brachytherapy and Androgen Deprivation in Patients With Prostate Cancer

    SciTech Connect

    Lilleby, Wolfgang; Tafjord, Gunnar; Raabe, Nils K.

    2012-07-01

    Purpose: To evaluate outcome (overall survival [OS], the actuarial 5-year cancer-specific survival [CSS], disease-free survival [DFS], biochemical failure-free survival [BFS]), complications and morbidity in patients treated with high-dose-rate brachytherapy (HDR-BT) boost and hormonal treatment with curative aims. Methods: Between 2004 and 2009, 275 prospectively followed pN0/N0M0 patients were included: 19 patients (7%) with T2, Gleason score 7 and prostate-specific antigen (PSA) <10 and 256 patients (93%) with T3 or Gleason score 8-10 or PSA >20 received multimodal treatment with conformal four-field radiotherapy (prostate/vesiculae 2 Gy Multiplication-Sign 25) combined with HDR-BT (iridium 192; prostate 10 Gy Multiplication-Sign 2) with long-term androgen deprivation therapy (ADT). Results: After a median observation time of 44.2 months (range, 10.4-90.5 months) 12 patients had relapsed clinically and/or biochemically and 10 patients were dead, of which 2 patients died from prostate cancer. Five-year estimates of BFS, CSS, DFS, and OS rates were 98.5%, 99.3%, 95.6%, and 96.3%, respectively. None of the patients with either Gleason score <8 or with intermediate risk profile had relapsed. The number of HDR-BT treatments was not related to outcome. Despite of age (median, 65.7 years; range, 45.7-77 years) and considerable pretreatment comorbidity in 39 of 275 patients, Genitourinary treatment-related morbidity was moderate with long-lasting Radiation Therapy Oncology Group Grade 2 voiding problems in 26 patients (9.5%) and occasionally mucous discharge in 20 patients (7%), none with Grade >2 for gastrointestinal at follow-up. Complications during implantations were related to pubic arch interference (4 patients) and lithotomy time, causing 2 patients to develop compartment syndrome. Conclusion: Despite still preliminary observations, our 5-year outcome estimates favor the implementation of high-dose-rate brachytherapy in high-risk patients combined with conformal

  12. How Can Men Destined for Biochemical Failure After Androgen Deprivation and Radiotherapy Be Identified Earlier?

    SciTech Connect

    D'Ambrosio, David J.; Ruth, Karen; Horwitz, Eric M.; Uzzo, Robert G.; Pollack, Alan; Buyyounouski, Mark K.

    2008-04-01

    Purpose: The significance of prostate-specific antigen (PSA) increases during the recovery of androgen after androgen deprivation therapy (ADT) and radiotherapy for prostate cancer is not well understood. This study sought to determine whether the initial PSA increase from undetectable after completion of all treatment predicts for eventual biochemical failure (BF). Methods and Materials: Between July 1992 and March 2004, 163 men with a Gleason score of 8-10 or initial PSA level >20 ng/mL, or Stage T3 prostate cancer were treated with radiotherapy (median dose, 76 Gy) and ADT and achieved an undetectable PSA level. The first detectable PSA level after the cessation of ADT was defined as the PSA sentinel rise (SR). A PSA-SR of >0.25, >0.5, >0.75, and >1.0 ng/mL was studied as predictors of BF (nadir plus 2 ng/mL). Cox proportional hazards models were used for univariate and multivariate analyses for BF adjusting for pretreatment differences in Gleason score, stage, PSA level (continuous), dose (continuous), and ADT duration (<12 vs. {>=}12 months). Results: Of the 163 men, 41 had BF after therapy. The median time to BF was 25 months (range, 4-96). The 5-year BF rate stratified by a PSA-SR of {<=}0.25 vs. >0.25 ng/mL was 28% vs. 43% (p = 0.02), {<=}0.5 vs. >0.5 ng/mL was 30% vs. 56% (p = 0.0003), {<=}0.75 vs. >0.75 ng/mL was 29% vs. 66% (p < 0.0001), and {<=}1.0 vs. >1.0 ng/mL was 29% vs. 75% (p < 0.0001). All four PSA-SRs were independently predictive of BF on multivariate analysis. Conclusion: The PSA-SR predicts for BF. A PSA-SR of >0.5 ng/mL can be used for early identification of men at greater risk of BF.

  13. Sleep deprivation predisposes liver to oxidative stress and phospholipid damage: a quantitative molecular imaging study

    PubMed Central

    Chang, Hung-Ming; Mai, Fu-Der; Chen, Bo-Jung; Wu, Un-In; Huang, Yi-Lun; Lan, Chyn-Tair; Ling, Yong-Chien

    2008-01-01

    Sleep disorders are associated with an increased rate of various metabolic disturbances, which may be related to oxidative stress and consequent lipid peroxidation. Since hepatic phosphatidylcholine plays an important role in metabolic regulation, the aim of the present study was to determine phosphatidylcholine expression in the liver following total sleep deprivation. To determine the effects of total sleep deprivation, we used adult rats implanted for polygraphic recording. Phosphatidylcholine expression was examined molecularly by the use of time-of-flight secondary ion mass spectrometry, along with biochemical solid-phase extraction. The parameters of oxidative stress were investigated by evaluating the hepatic malondialdehyde levels as well as heat shock protein 25 immunoblotting and immunohistochemistry. In normal rats, the time-of-flight secondary ion mass spectrometry spectra revealed specific peaks (m/z 184 and 224) that could be identified as molecular ions for phosphatidylcholine. However, following total sleep deprivation, the signals for phosphatidylcholine were significantly reduced to nearly one-third of the normal values. The results of solid-phase extraction also revealed that the phosphatidylcholine concentration was noticeably decreased, from 15.7 µmol g–1 to 9.4 µmol g–1, after total sleep deprivation. By contrast, the biomarkers for oxidative stress were drastically up-regulated in the total sleep deprivation-treated rats as compared with the normal ones (4.03 vs. 1.58 nmol mg–1 for malondialdehyde levels, and 17.1 vs. 6.7 as well as 1.8 vs. 0.7 for heat shock protein 25 immunoblotting and immunoreactivity, respectively). Given that phosphatidylcholine is the most prominent component of all plasma lipoproteins, decreased expression of hepatic phosphatidylcholine following total sleep deprivation may be attributed to the enhanced oxidative stress and the subsequent lipid peroxidation, which would play an important role in the formation

  14. Dehydroepiandrosterone protects male and female hippocampal neurons and neuroblastoma cells from glucose deprivation.

    PubMed

    Vieira-Marques, Claudia; Arbo, Bruno Dutra; Ruiz-Palmero, Isabel; Ortiz-Rodriguez, Ana; Ghorbanpoor, Samar; Kucharski, Luiz Carlos; Arevalo, Maria A; Garcia-Segura, Luis Miguel; Ribeiro, Maria Flávia M

    2016-08-01

    Dehydroepiandrosterone (DHEA) modulates neurogenesis, neuronal function, neuronal survival and metabolism, enhancing mitochondrial oxidative capacity. Glucose deprivation and hypometabolism have been implicated in the mechanisms that mediate neuronal damage in neurological disorders, and some studies have shown that these mechanisms are sexually dimorphic. It was also demonstrated that DHEA is able to attenuate the hypometabolism that is related to some neurodegenerative diseases, eliciting neuroprotective effects in different experimental models of neurodegeneration. The aim of this study was to evaluate the effect of DHEA on the viability of male and female hippocampal neurons and SH-SY5Y neuroblastoma cells exposed to glucose deprivation. It was observed that after 12h of pre-treatment, DHEA was able to protect SH-SY5Y cells from glucose deprivation for 6h (DHEA 10(-12), 10(-8) and 10(-6)M) and 8h (DHEA 10(-8)M). In contrast, DHEA was not neuroprotective against glucose deprivation for 12 or 24h. DHEA (10(-8)M) also protected SH-SY5Y cells when added together or even 1h after the beginning of glucose deprivation (6h). Furthermore, DHEA (10(-8)M) also protected primary neurons from both sexes against glucose deprivation. In summary, our findings indicate that DHEA is neuroprotective against glucose deprivation in human neuroblastoma cells and in male and female mouse hippocampal neurons. These results suggest that DHEA could be a promising candidate to be used in clinical studies aiming to reduce neuronal damage in people from both sexes. PMID:27174000

  15. The food retail environment and area deprivation in Glasgow City, UK

    PubMed Central

    Macdonald, Laura; Ellaway, Anne; Macintyre, Sally

    2009-01-01

    It has previously been suggested that deprived neighbourhoods within modern cities have poor access to general amenities, for example, fewer food retail outlets. Here we examine the distribution of food retailers by deprivation in the City of Glasgow, UK. We obtained a list of 934 food retailers in Glasgow, UK, in 2007, and mapped these at address level. We categorised small areas (data zones) into quintiles of area deprivation using the 2006 Scottish Index of Multiple Deprivation Income sub-domain score. We computed mean number of retailers per 1000 residents per data zone, and mean network distance to nearest outlet from data zone centroid, for all retailers combined and for each of seven categories of retailer separately (i.e. bakers, butchers, fruit and vegetable sellers, fishmongers, convenience stores, supermarkets and delicatessens). The most deprived quintile (of areas) had the greatest mean number of total food retailers per 1000 residents while quintile 1 (least deprived) had the least, and this difference was statistically significant (Chi-square p < 0.01). The closest mean distance to the nearest food retailer was within quintile 3 while the furthest distance was within quintile 1, and this was also statistically significant (Chi-square p < 0.01). There was variation in the distribution of the seven different types of food retailers, and access to amenities depended upon the type of food retailer studied and whether proximity or density was measured. Overall the findings suggested that deprived neighbourhoods within the City of Glasgow did not necessarily have fewer food retail outlets. PMID:19660114

  16. Donepezil Improves Episodic Memory in Young Individuals Vulnerable to the Effects of Sleep Deprivation

    PubMed Central

    Chuah, Lisa Y.M.; Chong, Delise L.; Chen, Annette K.; Rekshan, William R.; Tan, Jiat-Chow; Zheng, Hui; Chee, Michael W.L.

    2009-01-01

    Study Objectives: We investigated if donepezil, a long-acting orally administered cholinesterase inhibitor, would reduce episodic memory deficits associated with 24 h of sleep deprivation. Design: Double-blind, placebo-controlled, crossover study involving 7 laboratory visits over 2 months. Participants underwent 4 functional MRI scans; 2 sessions (donepezil or placebo) followed a normal night's sleep, and 2 sessions followed a night of sleep deprivation. Setting: The study took place in a research laboratory. Participants: 26 young, healthy volunteers with no history of any sleep, psychiatric, or neurologic disorders. Interventions: 5 mg of donepezil was taken once daily for approximately 17 days. Measurements and Results: Subjects were scanned while performing a semantic judgment task and tested for word recognition outside the scanner 45 minutes later. Sleep deprivation increased the frequency of non-responses at encoding and impaired delayed recognition. No benefit of donepezil was evident when participants were well rested. When sleep deprived, individuals who showed greater performance decline improved with donepezil, whereas more resistant individuals did not benefit. Accompanying these behavioral effects, there was corresponding modulation of task-related activation in functionally relevant brain regions. Brain regions identified in relation to donepezil-induced alteration in non-response rates could be distinguished from regions relating to improved recognition memory. This suggests that donepezil can improve delayed recognition in sleep-deprived persons by improving attention as well as enhancing memory encoding. Conclusions: Donepezil reduced decline in recognition performance in individuals vulnerable to the effects of sleep deprivation. Additionally, our findings demonstrate the utility of combined fMRI–behavior evaluation in psychopharmacological studies. Citation: Chuah LYM; Chong DL; Chen AK; Rekshan WR; Tan JC; Zheng H; Chee MWL. Donepezil

  17. Gender Differences in Sleep Deprivation Effects on Risk and Inequality Aversion: Evidence from an Economic Experiment

    PubMed Central

    Ferrara, Michele; Bottasso, Anna; Tempesta, Daniela; Carrieri, Marika; De Gennaro, Luigi; Ponti, Giovanni

    2015-01-01

    Excessive working hours—even at night—are becoming increasingly common in our modern 24/7 society. The prefrontal cortex (PFC) is particularly vulnerable to the effects of sleep loss and, consequently, the specific behaviors subserved by the functional integrity of the PFC, such as risk-taking and pro-social behavior, may be affected significantly. This paper seeks to assess the effects of one night of sleep deprivation on subjects’ risk and social preferences, which are probably the most explored behavioral domains in the tradition of Experimental Economics. This novel cross-over study employs thirty-two university students (gender-balanced) participating to 2 counterbalanced laboratory sessions in which they perform standard risk and social preference elicitation protocols. One session was after one night of undisturbed sleep at home, and the other was after one night of sleep deprivation in the laboratory. Sleep deprivation causes increased sleepiness and decreased alertness in all subjects. After sleep loss males make riskier decisions compared to the rested condition, while females do the opposite. Females likewise show decreased inequity aversion after sleep deprivation. As for the relationship between cognitive ability and economic decisions, sleep deprived individuals with higher cognitive reflection show lower risk aversion and more altruistic behavior. These results show that one night of sleep deprivation alters economic behavior in a gender-sensitive way. Females’ reaction to sleep deprivation, characterized by reduced risky choices and increased egoism compared to males, may be related to intrinsic psychological gender differences, such as in the way men and women weigh up probabilities in their decision-making, and/or to the different neurofunctional substrate of their decision-making. PMID:25793869

  18. Performance monitoring following total sleep deprivation: effects of task type and error rate.

    PubMed

    Renn, Ryan P; Cote, Kimberly A

    2013-04-01

    There is a need to understand the neural basis of performance deficits that result from sleep deprivation. Performance monitoring tasks generate response-locked event-related potentials (ERPs), generated from the anterior cingulate cortex (ACC) located in the medial surface of the frontal lobe that reflect error processing. The outcome of previous research on performance monitoring during sleepiness has been mixed. The purpose of this study was to evaluate performance monitoring in a controlled study of experimental sleep deprivation using a traditional Flanker task, and to broaden this examination using a response inhibition task. Forty-nine young adults (24 male) were randomly assigned to a total sleep deprivation or rested control group. The sleep deprivation group was slower on the Flanker task and less accurate on a Go/NoGo task compared to controls. General attentional impairments were evident in stimulus-locked ERPs for the sleep deprived group: P300 was delayed on Flanker trials and smaller to Go-stimuli. Further, N2 was smaller to NoGo stimuli, and the response-locked ERN was smaller on both tasks, reflecting neurocognitive impairment during performance monitoring. In the Flanker task, higher error rate was associated with smaller ERN amplitudes for both groups. Examination of ERN amplitude over time showed that it attenuated in the rested control group as error rate increased, but such habituation was not apparent in the sleep deprived group. Poor performing sleep deprived individuals had a larger Pe response than controls, possibly indicating perseveration of errors. These data provide insight into the neural underpinnings of performance failure during sleepiness and have implications for workplace and driving safety. PMID:23384887

  19. EEG quantification of alertness: methods for early identification of individuals most susceptible to sleep deprivation

    NASA Astrophysics Data System (ADS)

    Berka, Chris; Levendowski, Daniel J.; Westbrook, Philip; Davis, Gene; Lumicao, Michelle N.; Olmstead, Richard E.; Popovic, Miodrag; Zivkovic, Vladimir T.; Ramsey, Caitlin K.

    2005-05-01

    Electroencephalographic (EEG) and neurocognitive measures were simultaneously acquired to quantify alertness from 24 participants during 44-hours of sleep deprivation. Performance on a three-choice vigilance task (3C-VT), paired-associate learning/memory task (PAL) and modified Maintenance of Wakefulness Test (MWT), and sleep technician-observed drowsiness (eye-closures, head-nods, EEG slowing) were quantified. The B-Alert system automatically classifies each second of EEG on an alertness/drowsiness continuum. B-Alert classifications were significantly correlated with technician-observations, visually scored EEG and performance measures. B-Alert classifications during 3C-VT, and technician observations and performance during the 3C-VT and PAL evidenced progressively increasing drowsiness as a result of sleep deprivation with a stabilizing effect observed at the batteries occurring between 0600 and 1100 suggesting a possible circadian effect similar to those reported in previous sleep deprivation studies. Participants were given an opportunity to take a 40-minute nap approximately 24-hours into the sleep deprivation portion of the study (i.e., 7 PM on Saturday). The nap was followed by a transient period of increased alertness. Approximately 8 hours after the nap, behavioral and physiological measures of drowsiness returned to levels prior to the nap. Cluster analysis was used to stratify individuals into three groups based on their level of impairment as a result of sleep deprivation. The combination of B-Alert and neuro-behavioral measures may identify individuals whose performance is most susceptible to sleep deprivation. These objective measures could be applied in an operational setting to provide a "biobehavioral assay" to determine vulnerability to sleep deprivation.

  20. Gender differences in sleep deprivation effects on risk and inequality aversion: evidence from an economic experiment.

    PubMed

    Ferrara, Michele; Bottasso, Anna; Tempesta, Daniela; Carrieri, Marika; De Gennaro, Luigi; Ponti, Giovanni

    2015-01-01

    Excessive working hours--even at night--are becoming increasingly common in our modern 24/7 society. The prefrontal cortex (PFC) is particularly vulnerable to the effects of sleep loss and, consequently, the specific behaviors subserved by the functional integrity of the PFC, such as risk-taking and pro-social behavior, may be affected significantly. This paper seeks to assess the effects of one night of sleep deprivation on subjects' risk and social preferences, which are probably the most explored behavioral domains in the tradition of Experimental Economics. This novel cross-over study employs thirty-two university students (gender-balanced) participating to 2 counterbalanced laboratory sessions in which they perform standard risk and social preference elicitation protocols. One session was after one night of undisturbed sleep at home, and the other was after one night of sleep deprivation in the laboratory. Sleep deprivation causes increased sleepiness and decreased alertness in all subjects. After sleep loss males make riskier decisions compared to the rested condition, while females do the opposite. Females likewise show decreased inequity aversion after sleep deprivation. As for the relationship between cognitive ability and economic decisions, sleep deprived individuals with higher cognitive reflection show lower risk aversion and more altruistic behavior. These results show that one night of sleep deprivation alters economic behavior in a gender-sensitive way. Females' reaction to sleep deprivation, characterized by reduced risky choices and increased egoism compared to males, may be related to intrinsic psychological gender differences, such as in the way men and women weigh up probabilities in their decision-making, and/or to the different neurofunctional substrate of their decision-making. PMID:25793869

  1. Does the effect of gender modify the relationship between deprivation and mortality?

    PubMed Central

    2012-01-01

    Background In this study we propose improvements to the method of elaborating deprivation indexes. First, in the selection of the variables, we incorporated a wider range of both objective and subjective measures. Second, in the statistical methodology, we used a distance indicator instead of the standard aggregating method principal component analysis. Third, we propose another methodological improvement, which consists in the use of a more robust statistical method to assess the relationship between deprivation and health responses in ecological regressions. Methods We conducted an ecological small-area analysis based on the residents of the Metropolitan region of Barcelona in the period 1994–2007. Standardized mortality rates, stratified by sex, were studied for four mortality causes: tumor of the bronquial, lung and trachea, diabetes mellitus type II, breast cancer, and prostate cancer. Socioeconomic conditions were summarized using a deprivation index. Sixteen socio-demographic variables available in the Spanish Census of Population and Housing were included. The deprivation index was constructed by aggregating the above-mentioned variables using the distance indicator, DP2. For the estimation of the ecological regression we used hierarchical Bayesian models with some improvements. Results At greater deprivation, there is an increased risk of dying from diabetes for both sexes and of dying from lung cancer for men. On the other hand, at greater deprivation, there is a decreased risk of dying from breast cancer and lung cancer for women. We did not find a clear relationship in the case of prostate cancer (presenting an increased risk but only in the second quintile of deprivation). Conclusions We believe our results were obtained using a more robust methodology. First off, we have built a better index that allows us to directly collect the variability of contextual variables without having to use arbitrary weights. Secondly, we have solved two major problems

  2. Inhibition of thermal tachypnoea in rabbits following exposure to cold and water deprivation.

    PubMed Central

    Maskrey, M; Nicol, S C

    1975-01-01

    1. Rabbits were clipped and exposed in turn to four environmental conditions: control (C), cold exposure (CE), water deprivation (WD) and water deprivation and cold exposure together (WD/CE). 2. Following each type of treatment, the rabbits were exposed for 1 hr to an ambient temperature (Ta) of 35 degrees C. During this time, respiratory frequency (RF), rectal temperature (Tre), activity and oxygen consumption (V02) were recorded. 3. It was found that under both cold exposure and water deprivation conditions, the mean respiratory frequency during the first 30 min of heat exposure was reduced when compared with controls. This was associated with a delay in the onset of thermal tachypnoea. Under conditions of water deprivation and cold exposure together, the mean respiratory frequency was further reduced and the length of the delay was increased. 4. Previous cold exposure led to an increase in the V02 measured at 35 degrees C, whereas the V02, after water deprivation and water deprivation and cold exposure together were not significantly different from the control. 5. Neither the initial Tre nor the change in the Tre during the course of the heat exposure were significantly different from the controls under any of the experimental conditions. 6. It is concluded that both water deprivation and previous cold exposure cause a block to panting in the heat and that the blocking mechanisms involved are closely interrelated. It is also concluded that neither the metabolic rate of the animal nor its initial or final Tre are important factors in determing the degree to which thermal tachypnoea is inhibited. PMID:1206541

  3. Psychological Effect of an Analogue Traumatic Event Reduced by Sleep Deprivation

    PubMed Central

    Porcheret, Kate; Holmes, Emily A.; Goodwin, Guy M.; Foster, Russell G.; Wulff, Katharina

    2015-01-01

    Study Objective: To examine the effect of sleep deprivation compared to sleep, immediately after experimental trauma stimuli on the development of intrusive memories to that trauma stimuli. Design: Participants were exposed to a film with traumatic content (trauma film). The immediate response to the trauma film was assessed, followed by either total sleep deprivation (sleep deprived group, N = 20) or sleep as usual (sleep group, N = 22). Twelve hours after the film viewing the initial psychological effect of the trauma film was measured and for the subsequent 6 days intrusive emotional memories related to the trauma film were recorded in daily life. Setting: Academic sleep laboratory and participants' home environment. Participants: Healthy paid volunteers. Measurements and results: On the first day after the trauma film, the psychological effect as assessed by the Impact of Event Scale – Revised was lower in the sleep deprived group compared to the sleep group. In addition, the sleep deprived group reported fewer intrusive emotional memories (mean 2.28, standard deviation [SD] 2.91) compared to the sleep group (mean 3.76, SD 3.35). Because habitual sleep/circadian patterns, psychological health, and immediate effect of the trauma film were similar at baseline for participants of both groups, the results cannot be accounted for by pre-existing inequalities between groups. Conclusions: Our findings suggest that sleep deprivation on one night, rather than sleeping, reduces emotional effect and intrusive memories following exposure to experimental trauma. Citation: Porcheret K, Holmes EA, Goodwin GM, Foster RG, Wulff K. Psychological effect of an analogue traumatic event reduced by sleep deprivation. SLEEP 2015;38(7):1017–1025. PMID:26118556

  4. Factors of deprivation associated with dental caries in young children.

    PubMed

    Gratrix, D; Holloway, P J

    1994-06-01

    Quantitative and qualitative data were collected on the communities in the Tameside and Glossop Health Authority district served by the five primary schools with the highest prevalences of dental caries among their 5-year-old children and contrasted with similar information from communities served by five schools whose 5-year-old pupils had the lowest prevalences of caries. Quantitative data were collected from a variety of sources including the health and education authorities, and qualitative information was gathered by interviewing health and education personnel with special knowledge of the primary and pre-school children involved. It was found that communities with a high caries activity among their primary school children had lower proportions of babies of normal birth weight and uptake of poliomyelitis vaccination, while more children were born to single parent families. They also had lower percentages of private housing, homes with a car and households in social classes 1 and 2. The high caries schools had more children receiving clothing allowances and free school meals. The communities they served had higher Townsend mean deprivation Z scores and lower percentages of crime rates per household. The high caries communities tended to bottle feed their babies, wean them earlier, use infant feeding bottles longer and give babies fruit juices more regularly. The parents in the high caries communities were reported to have higher proportions of social and financial problems, were less likely to form parent-teacher associations, their children had poorer attendance and punctuality records, worse behaviour and greater consumption of confectionery after school.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8044712

  5. Developing a new small-area measure of deprivation using 2001 and 2011 census data from Scotland.

    PubMed

    Allik, Mirjam; Brown, Denise; Dundas, Ruth; Leyland, Alastair H

    2016-05-01

    Material deprivation contributes to inequalities in health; areas of high deprivation have higher rates of ill-health. How deprivation is measured has a great impact on its explanatory power with respect to health. We compare previous deprivation measures used in Scotland and proposes a new deprivation measure using the 2001 and 2011 Scottish census data. We calculate the relative index of inequality (RII) for self-reported health and mortality. While across all age groups different deprivation measures provide similar results, the assessment of health inequalities among those aged 20-29 differs markedly according to the deprivation measure. In 2011 the RII for long-term health problem for men aged 20-24 was only 0.71 (95% CI 0.60-0.83) using the Carstairs score, but 1.10 (0.99-1.21) for the new score and 1.13 (1.03-1.24) for the income domain of Scottish Index of Multiple Deprivation (SIMD). The RII for mortality in that age group was 1.25 (0.89-1.58) for the Carstairs score, 1.69 (1.35-2.02) for the new measure and 1.76 (1.43-2.08) for SIMD. The results suggest that researchers and policy makers should consider the suitability of deprivation measures for different social groups. PMID:27082656

  6. Sleep deprivation impairs the extinction of cocaine-induced environmental conditioning in mice.

    PubMed

    Berro, L F; Hollais, A W; Patti, C L; Fukushiro, D F; Mári-Kawamoto, E; Talhati, F; Costa, J M; Zanin, K A; Lopes-Silva, L B; Ceccon, L M; Santos, R; Procópio-Souza, R; Trombin, T F; Yokoyama, T S; Wuo-Silva, R; Tufik, S; Andersen, M L; Frussa-Filho, R

    2014-09-01

    Persistence of a drug-environment conditioning induced by repeated psychostimulant treatment is thought to play a key role in the addictive cycle. In addition, sleep disorders are a common feature in patients with addictive disorders. Sleep deprivation shares similar neurobiological effects with psychostimulants. Therefore, we investigated whether sleep deprivation would impair the extinction of previously established conditioning between the drug effect and the environmental cues. Four cohorts of male adult mice underwent a behavioral sensitization procedure pairing drug (cocaine at 15 mg/kg, i.p.) or saline with environment (open-field apparatus). The extinction of conditioned locomotion was evaluated after control (home-cage maintained) or sleep deprivation (gentle handling method for 6h) conditions. Sleep deprivation both postponed the initiation and impaired the completeness of extinction of the conditioned locomotion promoted by previous drug-environment conditioning in cocaine-sensitized animals. While the cocaine control group required 5 free-drug sessions of exposure to the open-field apparatus to complete extinction of conditioned locomotion, the cocaine pre-treated group that experienced sleep deprivation before each extinction session still significantly differed from its respective control group on Day 5 of extinction. The possibility that the sleep condition can influence the extinction of a long-lasting association between drug effects and environmental cues can represent new outcomes for clinically relevant phenomena. PMID:24836180

  7. Release of brain amino acids during hyposmolar stress and energy deprivation.

    PubMed

    Haugstad, T S; Langmoen, I A

    1996-04-01

    The release of 10 amino acids from rat hippocampal slices during exposure to hyposmotic stress or energy deprivation was measured by high-performance liquid chromatography. Exposing the slices to hyposmotic stress by lowering extracellular NaCl caused a 10-fold release of taurine (p < 0.01) and over a twofold increase of gamma-aminobutyric acid (GABA) and glutamate (p < 0.01). These changes were reversed by mannitol. Exposure to combined glucose and oxygen deprivation (energy deprivation) caused a 50-fold increase in the release of GABA, a 40-fold increase in glutamate release (p < 0.01), and a twofold to sixfold increase in taurine, aspartate, glycine, asparagine, serine, and alanine release (p < 0.05) but no change in glutamine. Energy deprivation increased the water content by 21%. Mannitol blocked this increase and further enhanced the release of glutamate and aspartate (p < 0.01) but not of GABA. The permissivity of the amino acids was plotted against the pI (pH at isoelectric point) and hydropathy indexes. Energy deprivation increased the permissivity in the following order: acidic > neutral > basic. Among neutral amino acids, permissivity increased with increasing hydrophobicity. These results indicate that the mechanisms of amino acid release are different during cerebral ischemia and hyposmotic stress. PMID:8829565

  8. Socioeconomic deprivation, perceived neighborhood factors, and cortisol responses to induced stress among healthy adults

    PubMed Central

    Barrington, Wendy E.; Stafford, Mai; Hamer, Mark; Beresford, Shirley A.A.; Koepsell, Thomas; Steptoe, Andrew

    2014-01-01

    Associations between measures of neighborhood socioeconomic deprivation and health have been identified, yet work is needed to uncover explanatory mechanisms. One hypothesized pathway is through stress, yet the few studies that have evaluated associations between characteristics of deprived neighborhoods and biomarkers of stress are mixed. This study evaluated whether objectively measured neighborhood socioeconomic deprivation and individual perceived neighborhood characteristics (i.e. social control and fear of crime) impacted cortisol responses to an induced stressor among older healthy adults. Data from Heart Scan, a sub-study of the Whitehall II cohort, were used to generate multilevel piecewise growth-curve models of cortisol trajectories after a laboratory stressor accounting for neighborhood and demographic characteristics. Neighborhood socioeconomic deprivation was significantly associated with individual perceptions of social control and fear of crime in the neighborhood while an association with blunted cortisol reactivity was only evidence among women. Social control was significantly associated with greater cortisol reactivity and mediation between neighborhood deprivation and cortisol reactivity was suggested among women. These findings support a gender-dependent role of neighborhood in stress process models of health. PMID:24603009

  9. Neighbourhood deprivation and very preterm birth in an English and French cohort

    PubMed Central

    2013-01-01

    Background Social factors affect the risk of very preterm birth and may affect subsequent outcomes in those born preterm. We assessed the influence of neighbourhood socio-economic characteristics on the risk and outcomes of singleton very preterm birth (<32 weeks of gestation) in two European regions with different health systems. Methods Live births (n=1118) from a population-based cohort of very preterm infants in 2003 in Trent (UK) and Ile-de-France (France) regions were geocoded to their neighbourhood census tracts. Odds ratios for very preterm singleton birth by neighbourhood characteristics (unemployment rate, proportion manual workers, proportion with high school education only, non home ownership) were computed using infants enumerated in the census as a control population. The impact of neighbourhood variables was further assessed by pregnancy and delivery characteristics and short term infant outcomes. Results Risk of very preterm singleton birth was higher in more deprived neighbourhoods in both regions (OR between 2.5 and 1.5 in the most versus least deprived quartiles). No consistent associations were found between neighbourhood deprivation and maternal characteristics or health outcomes for very preterm births, although infants in more deprived neighbourhoods were less likely to be breastfed at discharge. Conclusions Neighbourhood deprivation had a strong consistent impact on the risk of singleton very preterm birth in two European regions, but did not appear to be associated with maternal characteristics or infant outcomes. Differences in breastfeeding at discharge suggest that socio-economic factors may affect long term outcomes. PMID:23617598

  10. IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by the AAR pathway.

    PubMed

    Malkani, Niyati; Jansson, Thomas; Gupta, Madhulika B

    2015-09-01