***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Approximately 30 % of breast cancer survivors report persistent fatigue of unknown origin . We have previously shown that cancer-related fatigue is associated with alterations in immunological parameters and serum cortisol levels in breast cancer survivors . The current study examined the diurnal rhythm of salivary cortisol in fatigued and non-fatigued breast cancer survivors .  Salivary cortisol measures  were obtained from breast cancer survivors with persistent fatigue ( n=13 ) and a control group of non-fatigued survivors ( n=16 ) . Participants  collected saliva sample s upon awakening and at 1200 , 1700 , and 2200 h on two consecutive days . Diurnal cortisol slope for each day was determined by linear regression of log-transformed cortisol values on collection time and analyzed using multi-level modeling . Fatigued breast cancer survivors had a significantly flatter cortisol slope than non-fatigued survivors , with a less rapid decline in cortisol levels in the evening hours . At the individual patient level , survivors who reported the highest levels of fatigue also had the flattest cortisol slopes . Group differences remained significant in analyses controlling for demographic and medical factors , daily health behaviors , and other potential confounds ( e.g. depressed mood , body mass index ) . Results suggest a subtle dysregulation in hypothalamic-pituitary-adrenal axis functioning in breast cancer survivors with persistent fatigue BACKGROUND Altered functioning of the hypothalamic-pituitary-adrenal axis ( HPA-axis ) has been associated with depression , but findings have been inconsistent . Among older depressed persons , both hyperactivity and hypo-activity of the HPA-axis were demonstrated . However , most studies were population -based studies , with single cortisol measurements , lacking insight into diurnal patterns of HPA-axis functioning . We aim to provide insight into functioning of the HPA-axis , assessed by various salivary cortisol sample s , in depressed older adults and non-depressed controls . METHODS Data were derived from the Netherl and s Study of Depression in Older Persons .  Cortisol levels  of older persons without a lifetime diagnosis of depression and /or anxiety ( n=109 ) were compared with older persons with a 6-month major depression diagnosis ( n=311 ) . ANCOVA analyses and r and om coefficient analysis on the four morning cortisol sample s were performed . A possible U-shaped association between cortisol and depression status was examined . RESULTS Depressed older persons showed higher morning cortisol levels at awakening ( T1 ) and a less dynamic awakening response compared to non-depressed older persons . Dexamethasone suppression did not differ across groups . No U-shaped association between HPA-axis activity and depression was observed . CONCLUSION We demonstrated a hypercortisolemic state and a diminished ability to respond to the stress of awakening among depressed older persons . Previously it was shown , that hypercortisolemic states may indicate a lifelong biological vulnerability for depression . Our findings exp and on previous literature by demonstrating that in older persons the HPA-axis may become less responsive to stress , culminating in a further dysregulation of the diurnal cortisol-rhythm , superimposed on - possibly lifelong - hypercortisolemic states Most prior studies in patients with premenstrual dysphoric disorder ( PMDD ) indicate a blunted hypothalamus – pituitary – adrenal axis function . However , the relationship between neuroactive progesterone metabolites , such as allopregnanolone , and hypothalamus – pituitary – adrenal ( HPA ) axis function in PMDD patients is relatively sparsely studied . The primary aims of this study were to assess diurnal variation in circulating cortisol and low-dose dexamethasone suppression in PMDD patients and healthy controls , and the relationship between these two HPA axis indices and allopregnanolone serum concentrations .  Twenty-six women with prospect ively defined PMDD and 30 healthy controls were recruited . Participants underwent diurnal sampling for cortisol serum concentrations and a low-dose dexamethasone suppression test . In addition , morning allopregnanolone serum concentrations were determined . There was no difference in diurnal secretion of cortisol and degree of dexamethasone suppression of cortisol between PMDD patients and healthy controls . However , PMDD patients with high allopregnanolone levels displayed blunted nocturnal cortisol levels in comparison with healthy controls who had low allopregnanolone serum concentrations . In women with PMDD , diurnal secretion of cortisol may be influenced by allopregnanolone levels of the luteal phase . This finding may be attributed to timing of blood sampling in the late luteal phase as well as the individual level of allopregnanolone but could potentially explain the discrepancies in results between studies examining HPA axis function in women with PMDD The aim of this prospect i ve quasi-experimental study was to assess the role of coping style as a factor moderating the relationship between  stress and sleep . Sleep of 36 students was assessed by means of actigraphy and daily logs during low-stress and high-stress periods . The high-stress period was the week that the students were evaluated for acceptance to graduate programs in clinical psychology . The low-stress period was a regular academic week . The students ' ways of coping were assessed during the baseline low-stress period using the COPE inventory .  Data analysis revealed that a high emotion-focused coping score was significantly predictive of reduction in sleep time from the low- to the high-stress period . These results suggest that coping style is a key factor in assessing the relationship between stress and sleep Objective : There is mounting evidence that psychosocial stress can delay wound healing , but this literature almost exclusively pertains to dermal wound healing . Many surgical procedures involve damage to mucosal tissues and the time course and the role of repair processes , such as inflammation , in the healing of these tissues are markedly different from those in dermal healing . Feelings of depression and social isolation are common among surgical patients , and the present study therefore investigated if these factors predict the rate of mucosal wound healing . Methods : Undergraduate students were invited to participate in the study if they reported high or low levels of loneliness or depressive symptoms , corresponding to the upper or lower quintile of their peer group . The  UCLA loneliness scale and the Beck Depression Inventory [ short form ] were used for this screening . A sample of 193 healthy young adults ( age range 18–31 years ) received a 3.5-mm circular wound on the oral hard palate , under local anesthesia .  Healing was monitored by daily videographs of the wound . Results : The median healing rate was 7 days . High dysphoric participants were , however , more likely to heal slower than this median healing rate ( odds ratio 3.57 ( 1.58–8.07 ) ; p < .001 ) . This association remained robust after correction for a broad range of demographic and behavioral variables , including gender , age , ethnicity , and health behaviors . High dysphoric individuals also exhibited significantly larger average wound sizes from day 2 post wounding onward . Loneliness and diurnal cortisol secretion ( measured over 5 days ) were unrelated to healing . Conclusion : Depressive symptoms predict the rate of mucosal wound healing in healthy young adults . We discuss potential pathways that warrant further investigation . HPA = hypothalamic-pituitary-adrenal ; BDI-sf = Beck Depression Inventory short form ; UCLA-R = Revised UCLA Loneliness Scale ; OR = odds ratio ; AUC = area under the curve Purpose Evidence has supported the association between psychological factors and cancer biology ; however , findings are equivocal on the role of psychosocial factors in cancer progression . This study generates a hypothesis of mechanistic variables by examining the clinical effects of psychosocial factors and cortisol dysregulation in patients with metastatic renal cell carcinoma ( RCC ) and examines associated activation of transcription control pathways . Methods Patients with metastatic RCC ( n = 217 ) were prospect ively enrolled in this study . Patients completed question naires ( Centers for Epidemiologic Studies – Depression ; SF-36 Health Status Survey ; Duke Social Support Index ; Coping Operations Preference Enquiry ; organized and non-organized religious activity ; and intrinsic religiosity ) , and provided blood and saliva sample s. Cortisol levels and  whole genome transcriptional profiling  were assessed to identify potential alterations in circadian rhythms and genomic pathways . Results Separate Cox regression models , controlling for disease risk category , revealed that CES-D scores ( p = 0.05 , HR = 1.5 , 95 % CI for HR : 1.00–2.23 ) and cortisol slope ( p = 0.002 ; HR = 1.9 ; 95%CI for HR : 1.27–2.97 ) were significantly associated with decreased survival . Only cortisol slope and risk category remained significant in the complete model . Functional genomic analyses linked depressive symptoms to increased expression of pro-inflammatory and pro-metastatic genes in circulating leukocytes . 116 transcripts were found to be upregulated by an average of 50 % or more in high CES-D patients , and 57 transcripts downregulated by at least 50 % . These changes were also found in the tumor in a subset of patients . Conclusion These findings identify depressive symptoms as a key predictor of survival in renal cell carcinoma patients with potential links to dysregulation of cortisol and inflammatory biology This study assessed the effects of modest sleep restriction and extension on  children 's neurobehavioral functioning ( NBF ) . The sleep of 77 children ( age : M = 10.6 years ; range = 9.1 - 12.2 years ) was monitored for 5 nights with activity monitors .  These children ( 39 boys and 38 girls ) were all attending regular 4th- and 6th- grade classes . Their NBF was assessed using computerized tests on the 2nd day of their normal sleep schedule . On the 3rd evening , the children were asked to extend or restrict their sleep by an hour on the following 3 nights . Their NBF was reassessed on the 6th day following the experimental sleep manipulation . Sleep restriction led to improved sleep quality and to reduced reported alertness . The sleep manipulation led to significant differential effects on NBF measures . These effects may have significant developmental and clinical implication Objectives : The aim of this study was to assess whether diurnal cortisol rhythm and cortisol stress reactivity were associated with  functional constipation and abdominal pain in infancy . Patients and Methods : This study was embedded in a subset of the Generation R Study , a prospect i ve cohort study from fetal life onward in Rotterdam , the Netherl and s. Data of infants between 14 and 24 months of age ( N = 483 ) were used .  Salivary cortisol diurnal rhythm and salivary cortisol stress reactivity after a Strange Situation Procedure were assessed at age 14 months . Data on functional constipation were available according to the Rome II criteria , and data on abdominal pain on the basis of the Abdominal Pain Index were available from question naire data at 24 months . Results : In the second year of life , 13 % of the infants had functional constipation and 17 % had abdominal pain . Only 4 % had symptoms of both functional constipation and abdominal pain . Diurnal cortisol rhythm did not differ significantly between children with and children without functional constipation and abdominal pain . Cortisol stress reactivity was slightly higher in infants with abdominal pain than in those without it , but this was not statistically significant ( odds ratio 1.41 ; 95 % confidence interval 0.46–4.31 ) . No association was found between the cortisol stress reactivity and functional constipation . Conclusions : Our results suggest that cortisol as a marker for stress does not play a major role in functional constipation or abdominal pain in infancy The aim of these analyses was to develop and describe easily implementable , yet information rich , approaches for analysis of the temporal profile of cortisol in human population s. A typical waking profile of cortisol in a sample of women aged 15 - 44 was parameterized by a piecewise linear regression model , implemented as a mixed model to accommo date repeated observations among individuals . The model was extended to distinguish characteristic cortisol profiles of obese women from those of non-obese women .  Sharp inflection points for the diurnal profile of cortisol were noted at 30 and 75 min past awakening . Obese women showed a slight tendency to have a less sharply rising and declining response to awakening than non-obese women Although data from animal studies show that early rearing experiences can have lasting effects on the hypothalamic-pituitary-adrenal ( HPA ) axis , little is known about the relationship between childhood parental loss and adult cortisol levels in humans . In the current study , 57 healthy adult men completed a telephone interview concerning parental loss or separations before age 17 .  Salivary cortisol measures , taken 10 times a day for 5 days in the daily environment , were available from an earlier study . Nine subjects had experienced the death of a parent during childhood . Compared to levels in 38 subjects who had experienced neither loss nor a separation  > two weeks , parental loss by death was associated with higher cortisol throughout the day ( F(1,44 ) = 4.73 , p = 0.035 ) . Men who had lost a parent scored no higher than those with no loss or separation on trait anxiety or current depressive symptoms , and the effect of parental loss on cortisol remained significant after controlling for these variables . Cortisol patterns in men who had been temporarily separated from one or both parents ( n = 10 ) were inconsistent . Limitations include 
    Output:
    
We argue that flatter diurnal cortisol slopes may both reflect and contribute to stress-related dysregulation of central and peripheral circadian mechanisms , with corresponding downstream effects on multiple aspects of biology , behavior , and health