***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: An altered function of the hypothalamic-pituitary-adrenal axis is assumed to be characteristic for Posttraumatic Stress Disorder ( PTSD ) , although there is inconsistent empirical evidence . Only few studies examined the awakening cortisol response and a daytime profile in PTSD .  Salivary cortisol levels were measured at seven intervals from awakening until 8 PM in trauma-exposed subjects with ( N=29 ) and without PTSD ( N=19 ) and in 15 non-exposed controls . While the three groups did not differ with respect to their first cortisol level immediately after awakening , the expected cortisol increase to awakening 15 - 60 min later was significantly lower in PTSD patients compared to non-PTSD subjects and healthy controls . This effect remained stable when trauma-exposed subjects with comorbid major depression were excluded from the analysis . A significant negative correlation between the overall cortisol secretion ( AUC(G ) ) and overall PTSD symptomatology and hyper-arousal symptoms was found . The findings are discussed in light of the hypothesis of a counterregulation of hyper-arousal symptoms and chronic stress in PTSD The purpose of the present investigation was to evaluate whether an anti-inflammatory effect together with an improvement of the regulation of the interaction between the inflammatory and stress responses underlies the clinical benefits of pelotherapy in osteoarthritis ( OA ) patients . This study evaluated the effects of a 10-day cycle of pelotherapy at the spa centre ‘ El Raposo ’ ( Spain ) in a group of 21 OA patients diagnosed with primary knee OA . Clinical assessment s included pain intensity using a visual analog scale ; pain , stiffness and physical function using the Western Ontario and McMaster Universities Arthritis Index ; and health-related quality of life using the EuroQol-5D question naire . Serum inflammatory cytokine levels ( IL-1β , TNF-α , IL-8 , IL-6 , IL-10 and TGF-β ) were evaluated using the Bio-Plex ® Luminex ® system . Circulating neuroendocrine-stress biomarkers , such as cortisol and extracellular 72 kDa heat shock protein ( eHsp72 ) , were measured by ELISA . After the cycle of mud therapy , OA patients improved the knee flexion angle and OA-related pain , stiffness and physical function , and they reported a better health-related quality of life . Serum concentrations of IL-1β , TNF-α , IL-8 , IL-6 and TGF-β , as well as eHsp72 , were markedly decreased . Besides , systemic levels of cortisol increased significantly . These results confirm that the clinical benefits of mud therapy may well be mediated , at least in part , by its systemic anti-inflammatory effects and neuroendocrine-immune regulation in OA patients . Thus , mud therapy could be an effective alternative treatment in the management of OA Our previous crossover r and omized trial suggested that spa therapy added to usual pharmacotherapy provides benefits that lasted 6 months over pharmacotherapy alone in rheumatoid arthritis patients . We now extend , and report the long-term results of that study . In the crossover trial , patients were r and omized to spa therapy first group or control first group ( first assignment , period 1 , 6 months ) ; after this period and washout phase ( 9 months ) , they crossed over to the other arm ( second assignment , period 2 , 6 months ) . In this long-term study , we now analyze the 15-month results of the first assignment , and 12-month results of the second assignment in the opposite side with a 6-month extension of the follow-up period . The clinical outcome measures were pain , patient and physician global assessment , Health Assessment Question naire , and Disease Activity Score-28 . The 15-month results of first assignment revealed no statistically significant differences between the groups in any of the efficacy outcomes ( p > 0.05 for all ) . The 12-month results for the second assignment after crossover revealed a statistically significant decrease between the groups regarding the patient global assessment scores ( p = 0.016 ) , physician global assessment scores ( p = 0.003 ) and swollen joints counts ( p = 0.030 ) ; however , no statistically significant difference was found between the groups in any of the other efficacy outcomes ( p > 0.05 for all ) . The short- and medium-term beneficial effects of the 2-week spa therapy added to the usual pharmacotherapy observed through the initial 6-month evaluation period may be maintained mildly to moderately to the 12-month mark in rheumatoid arthritis patients receiving conventional disease-modifying antirheumatic drugs . Further studies with a larger sample size are needed for the confirmation of the study results Both physical activity and relaxation have stress-relieving potential . This study investigates their combined impact on the relaxation response while considering participants ' initial stress level . In a r and omized cross-over trial , 81 healthy adults completed 4 types of short-term interventions for stress reduction , each lasting for 1 hr : ( 1 ) physical activity ( walking ) combined with resting , ( 2 ) walking combined with balneotherapy , ( 3 ) combined resting and balneotherapy , and ( 4 ) resting only .  Saliva cortisol , blood pressure , state of mood , and relaxation were measured preintervention and postintervention . Stress levels were determined by vali date d question naires . All interventions were associated with relaxation responses in the variables saliva cortisol , blood pressure , state of mood , and subjective relaxation . No significant differences were found regarding the reduction of salivary cortisol ( F = 1.30 ; p = .281 ) . The systolic blood pressure was reduced best when walking was combined with balneotherapy or resting ( F = 7.34 ; p < .001 ) . Participants with high stress levels ( n = 25 ) felt more alert after interventions including balneotherapy , whereas they reported an increase of tiredness when walking was combined with resting ( F = 3.20 ; p = .044 ) . Results suggest that combining physical activity and relaxation ( resting or balneotherapy ) is an advantageous short-term strategy for stress reduction as systolic blood pressure is reduced best while similar levels of relaxation can be obtained The placebo and nocebo effect is believed to be mediated by both cognitive and conditioning mechanisms , although little is known about their role in different circumstances . In this study , we first analyzed the effects of opposing verbal suggestions on experimental ischemic arm pain in healthy volunteers and on motor performance in Parkinsonian patients and found that verbally induced expectations of analgesia/hyperalgesia and motor improvement/worsening antagonized completely the effects of a conditioning procedure . We also measured the effects of opposing verbal suggestions on hormonal secretion and found that verbally induced expectations of increase/decrease of growth hormone ( GH ) and cortisol did not have any effect on the secretion of these hormones . However , if a preconditioning was performed with sumatriptan , a 5-HT1B/1D agonist that stimulates GH and inhibits cortisol secretion , a significant increase of GH and decrease of cortisol plasma concentrations were found after placebo administration , although opposite verbal suggestions were given . These findings indicate that verbally induced expectations have no effect on hormonal secretion , whereas they affect pain and motor performance . This suggests that placebo responses are mediated by conditioning when unconscious physiological functions such as hormonal secretion are involved , whereas they are mediated by expectation when conscious physiological processes such as pain and motor performance come into play , even though a conditioning procedure is performed Very few studies tested the effectiveness of spa therapy in older patients with osteoarthritis . Therefore , we aim ed to evaluate the short-term effects of spa therapy in patients aged 65 years and older with generalized , knee , hip , and cervical and lumbar spine osteoarthritis . In an observational retrospective study design at the Medical Ecology and Hydroclimatology Department of Istanbul Medical Faculty , we analyzed the records of 239 patients aged over 65 years with the diagnosis of all types of osteoarthritis who were prescribed a spa therapy course in some spa resorts in Turkey between 7 March 2002 and 31 December 2012 . They travelled to a spa resort where they stayed at a thermal spa hotel and followed the usual therapy packages for 2 weeks . Patients were assessed by an experienced physician within a week before the spa journey and within a week after the completion of the spa therapy . Compared with baseline in whole sample , statistically significant improvements were observed in pain ( visual analog scale , VAS ) , patient and physician global assessment s ( VAS ) , Health Assessment Question naire disability index ( HAQ-DI ) , Lequesne algofunctional index ( LAFI ) for knee , Western Ontario and McMaster Universities index ( WOMAC ) , Waddell disability index ( WDI ) , and Neck Pain and Disability Scale ( NPAD ) . According to Outcome Measures in Rheumatology — Osteoarthritis Research Society International ( OMERACT-OARSI ) Set of Responder Criteria , responder rate were 63.8 % ( 51/80 ) in generalized , 52 % ( 13/25 ) in knee , 50 % ( 2/4 ) in hip , 66.7 % ( 8/12 ) in lumbar , and 100 % ( 6/6 ) in cervical osteoarthritis subgroups . Spa therapy  improved pain and physical functional status in older patients with osteoarthritis , especially generalized osteoarthritis and multiple joint osteoarthritis with involvement of knee . This improvement was clinical ly important in majority of the patients . To confirm the results of this preliminary study , there is a need of a r and omized controlled clinical study comparing spa therapy with usual care in the elderly population with osteoarthritis Objectives : To investigated serum cortisol and serum dehydroepi and rosterone-sulphate ( DHEA-S ) levels between fibromyalgia ( FMS ) patients and a control group , and the effect of balneotherapy ( BT ) on these hormones . Methods : Seventy-two patients with FMS and 39 healthy volunteers were included in the study . This prospect i ve and cross-sectional study was carried out in the Medical Faculty , Physical Medicine and Rehabilitation Clinic , Cumhuriyet University , Cumhuriyet , Turkey between June 2012 and June 2013 . Patients were divided into 2 groups . There were 40 patients in the first group , consisting of BT and physical therapy ( PT ) administered patients . There were 32 FMS patients in the second group who were only administered PT .  Thirty-nine healthy volunteers were enrolled as a control group . Result : Cortisol was observed to be lower in FMS patients compared with the controls ( 10.10±4.08 μg/dL and 11.78±3.6 μg/dL ; p=0.033 ) . Serum DHEA-S level was observed to be lower in FMS patients compared with the controls ( 89.93±53.96 μg/dL and 143.15±107.92 μg/dL ; p=0.015 ) . Average serum cortisol levels of patients receiving BT were determined to be 9.95±3.20 μg/dL before treatment and 9.06±3.77μg/dL after treatment ; while average serum DHEA-S levels were 77.60±48.05 μg/dL before treatment , and 76.84±48.71 μg/dL after treatment . No significant changes were determined in serum cortisol and DHEA-S levels when measured again after BT and PT . Conclusion : Low levels of serum cortisol and DHEA-S were suggested to be associated with the physiopathology of FMS Activity of the hypothalamus pituitary adrenal ( HPA ) axis is characterized by a pronounced circadian rhythm . An acute increase in cortisol levels occurs after awakening in the morning with continuously declining levels over the course of the remaining day . The morning cortisol increase probably reflects an activational response of the HPA axis aim ed at preparing the body for the day . Some studies found patterns of enhanced or blunted waking cortisol responses observed under chronic stress , burnout , or post traumatic stress disorder . The present study wanted to characterize the morning cortisol response and the circadian cortisol day profile in a sample of six male patients with severe amnesia due to hypoxia , herpes simplex encephalitis or closed head injury . Age and gender matched relatives or friends served as controls  . Cortisol  was measured from saliva sample s collected at home on two consecutive days . The patients were woken up in the morning by their partners or caregivers . The morning cortisol increase typically observed in healthy subjects and also observed in the control group was absent in the amnesic patients . In contrast , a normal circadian day profile was found in the amnesic patients , with a pronounced circadian cortisol decrease . Further studies are needed to underst and the neurological or psychological mechanisms leading to a missing morning cortisol response in amnesic patients Moor mud applications in the form of packs and baths are widely used therapeutically as part of balneotherapy . They are commonly given as therapy for musculoskeletal disorders , with their thermo-physical effects being furthest studied . Moor baths are one of the key therapeutic elements in our recently developed and evaluated 3-week prevention program for subjects with high stress level and increased risk of developing a burnout syndrome . An embedded pilot study add-on to this core project was carried out to assess the relaxing effect of a single moor bath . During the prevention program , 78 participants received a total of seven moor applications  , each consisting of a moor bath ( 
    Output:
    
Our main findings suggest that balneotherapy may have the potential to influence cortisol levels in healthy subjects , in such a way as to improve stress resilience .
Spa therapy with or without included mud/peloid therapy demonstrated the same potential to influence cortisol levels also in sub-healthy subjects and in patients with a diagnosed disease .
Therefore , balneotherapy and spa therapy may be considered as useful interventions for the management of stress conditions .