***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 
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    ***EXAMPLES*** 
    Input: We examined whether the effects of intravenously injected insulin and glucose ( the physiological endogenous insulin production stimulus ) could be classically conditioned in healthy humans . We expected a conditioned blood glucose decrease to a conditioned stimulus ( CS ) previously paired with insulin and an , albeit lower , blood glucose decrease to a CS paired with glucose injection . In addition , we analyzed glucoregulatory hormone and symptom conditionability . Thirty healthy males were divided into three groups and were given the CS and an intravenous injection of either insulin ( 0.05 IU/kg ) in Group 1 , glucose ( 15 % , 0.5 g/kg ) in Group 2 , or placebo [ physiological saline ( 0.9 % ) ] in Group 3 during the acquisition phase on 4 days . All participants were given the olfactory CS ( rosewood-peppermint smell ) and placebo injection on Day 5 ( test ) . On Day 5 , the total blood glucose decrease tended to be higher in Group 1 than in Group 3 ( P<.10 ) , especially at CS presentation ( P<.10 ) and previous unconditioned hypoglycemia time-point ( P<.05 ) . The conditioned blood glucose decrease was statistically nonsignificant in Group 2 , but shortly after CS presentation , insulin level and blood glucose changes were negatively correlated in Groups 1 and 2 in contrast to positive correlation in Group 3 . Furthermore , Group 1 showed an increase in noradrenaline ( P<.05 ) , a temporarily delayed increase in growth hormone ( GH ; P<.05 ) , and an increase of autonomic and neuroglycopenic symptoms , reaching a medium and small effect size , respectively . Group 2 responded with an increase in cortisol ( P<.01 ) and neuroglycopenic symptoms ( P<.05 ) at the time-point of the previous unconditioned blood glucose minimum . To conclude , the effects of exogenously applied insulin can be conditioned in a reliable way . In correspondence with the lower intensity of the unconditioned stimulus ( US ) , conditioning effects with glucose- and , thus , endogenously produced insulin-are weaker but also reflect the actions of central insulin . Future studies will examine the diverse actions of insulin within the brain further The infusion of cytotoxic drugs in cancer patients is often accompanied by posttreatment nausea ( PN ) . In addition , patients complain about nausea prior to an infusion [ i.e. , anticipatory nausea ( AN ) ] . AN is mainly explained by classical conditioning , with the infusion as the unconditioned stimulus ( US ) and with the stimuli signaling the infusion as conditioned stimuli ( CS ) . Despite this conditioning etiology , a specifically derived therapy to attenuate the CS-US contingency is missing . The purpose of this study is to develop and to test an overshadowing procedure for prevention of AN , and also for the modification of PN intensity . Sixteen cancer patients were assigned to one of two groups : Overshadowing+ ( OV+ ) and Overshadowing- ( OV- ) . At the start of all infusions of two consecutive chemotherapy cycles A and B ( acquisition ) , OV+ subjects drank a saliently tasting beverage ( the overshadowing CS ) , whereas group OV- drank water . All patients received water in cycle C ( test ) . Self-reported symptoms and heart rates were recorded . As expected , in cycle C ( test ) , no patient of group OV+ showed AN , whereas two patients of group OV- developed AN . There was a tendency for a reduction of the intensity of PN , in terms of duration and latency after overshadowing , in cycle C : OV+ patients tended to show a shorter duration and a longer latency between end of infusion and PN onset . In OV- , there was a significantly larger heart rate deceleration in both measurement periods , in the anticipatory and the posttreatment measurement period . Data suggest to apply overshadowing for prevention of AN and modification of PN . Physiological markers of conditioned nausea are revealed . After its procedural implementation , the technique can be used in larger sample s now 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 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objective : To test the hypothesize that psoriasis patients treated under a partial schedule of pharmacologic ( corticosteroid ) reinforcement  would show less severe symptoms and relapse than those given the same amount of drug under st and ard conditions . Behavioral conditioning as an inherent component of many pharmacotherapeutic protocol s has never been examined . Methods : A double-blind , simple r and omization intervention was conducted with 46 patients from California and New York . Initially , lesions were treated with 0.1 % acetonide triamcinolone under st and ard treatment conditions . Thereafter , a St and ard Therapy group continued on continuous reinforcement ( active drug every treatment ) with 100 % of the initial dose ; Partial Reinforcement patients received a full dose 25 % to 50 % of the time and placebo medication other times ; Dose Control patients received continuous reinforcement with 25 % to 50 % of the initial dose . Results :  Severity of disease scores in California neither supported nor refuted the hypothesis . In New York , where there was no difference between Partial Reinforcement and Dose Control groups at baseline , partial reinforcement effected a greater reduction in lesion severity than Dose Control conditions and did not differ from St and ard Therapy patients receiving two to four times more drug . For the entire population , the frequency of relapse under partial reinforcement ( 26.7 % ) was lower than in Dose Control patients ( 61.5 % ) and did not differ from full-dose treatment ( 22.2 % ) . Conclusions : A partial schedule of pharmacotherapeutic reinforcement could maintain psoriasis patients with a cumulative amount of  corticosteroid  that was relatively ineffective when administered under st and ard treatment conditions . Conceivably , corticosteroid administration only one quarter or half as frequently as currently prescribed is sufficient to treat psoriasis . We posit , however , that these preliminary observations implicate conditioning processes in— and for the design of — regimens of pharmacotherapy . PSS = Psoriasis Severity Scale ; CS = conditioned stimulus ; UCS = unconditioned stimulus OBJECTIVE Classical conditioning of insulin effects was examined in healthy humans using a placebo-controlled design . This study examined whether subjects who experienced a conditioned stimulus ( CS ) paired with insulin in the acquisition phase of a conditioning protocol would show a conditioned decrease of blood glucose when receiving the CS with a placebo injection in the test phase . METHODS Twenty healthy male students were assigned either to group 1 , which received insulin ( 0.035 IU/kg i.v . ) , or to group 2 , which received i.v . saline on 4 consecutive days ( acquisition ) . On day 5 ( test ) , both groups were injected with saline . The CS was an olfactory stimulus . Blood glucose , serum insulin , plasma glucagon , plasma catecholamines , serum cortisol , and symptoms were repeatedly measured during each session . RESULTS In the test phase , group 1 reacted with a significantly larger decrease of blood glucose after presentation of the CS than group 2 . Within group 1 , a larger conditioned blood glucose decrease was associated with features that enhance classical conditioning ( ie , intensity of the unconditioned response and intensity of the CS ) . Furthermore , in group 1 , there was an increase of baseline insulin from day 1 to day 5 and a tendency for insulin reduction after CS presentation . Groups also tended to differ in cortisol and neuroglycopenic symptoms after CS presentation . CONCLUSIONS Conditioned effects in blood glucose are in accordance with the predictions . As a result of the exploratory analyses , our data also provide hints about conditioned changes in insulin , counterregulatory hormones , and symptoms Objectives : Pre-exposure to an environment in which a nausea-inducing body rotation will subsequently be given constitutes a latent inhibition procedure that might act to reduce anticipatory and postrotation nausea . Methods : This was tested in 24 healthy subjects r and omly assigned to receive no pre-exposure ( group 0 ) , a single pre-exposure ( group 1 ) , or three pre-exposures ( group 3 ) .  Rotation was st and ardized as 5 × 1 minute rotation , but the subjects could terminate it on request . Nausea was determined on a 7-item symptom rating scale before , during , and after rotation on days 3 and 4 , whereas anticipatory nausea was measured before presumed rotation on day 5 . Saliva cortisol and tumor necrosis factor & agr ; ( TNF-&agr ; ) levels were determined at baseline before , directly , and 15 and 30 minutes after rotation every day , and before presumed rotation on day 5 . Results : Pre-exposure significantly reduced the degree of anticipatory nausea on day 5 . Cortisol levels increased with rotation and were higher at baseline on days 4 and 5 , but subjects habituated from day 3 to day 4 ; levels were lower in women than in men . In contrast , TNF-&agr ; decreased with rotation but showed no habituation . For both cortisol and TNF-&agr ; , no effects on postrotational nausea were found . Conclusion : It is concluded that repetitive pre-exposure ( latent inhibition ) reduces anticipatory but not postrotation nausea ; behavioral measures ( rotation time ) and measures of acute stress ( cortisol , TNF-&agr ; ) do not respond to latent inhibition . Thus , Pavlovian conditioning rules are effective in healthy humans with anticipatory nausea but not with postrotation nausea . Hormonal responses — TNF-&agr ; decrease with stress , compensatory cortisol increase— and gender-related effects on learning and habituation are discussed with regard to psychophysiological and psychoimmunological processes . AN = anticipatory nausea ; CS = conditioned stimulus ; US = unconditioned stimulus ; CR = conditioned response ; PN = posttreatment nausea ; UR = unconditioned response ; TNF-&agr ; = tumor necrosis factor & agr ; ; RT = rotation tolerance ; MSSQ = motion sickness susceptibility question naire ; SR = symptom rating ; ANOVA = analysis of variance A classical Pavlovian paradigm pairing an olfactory cue with allergen challenge for a single training trial was used to produce conditioned histamine release and conditioned nasal airflow decrease in seasonal allergic rhinitis sufferers . There was no conditioned increase in subjective symptoms . Histamine release and airflow decrease showed evidence of extinction by a second test trial . A second study comparing the effects of the number of training trials showed that three training trials produced greater histamine release and airflow decrease than a single training trial , suggesting stronger effects with additional training Aims /hypothesisIn humans , the intranasal route allows insulin to reach the brain while maintaining peripheral euglycaemia . Our aims were to examine acute ( unconditioned ) effects of central insulin on normal-range blood glucose and hormones in men , and to find out whether the effects of intranasal insulin can be learnt via classical conditioning . Methods In a r and omised controlled trial , 32 healthy normal-weight men ( mean age 24.2 [ SEM 0.5 ] , mean BMI 22.4 [ 0.3 ] ) received a conditioned stimulus ( CS ) and six administrations of either soluble H-insulin 100 ( 20 U [ 0.2 ml ] ; group 1 ; n = 16 ) or vehicle ( 0.2 ml ; group 2 ; n = 16 ) on day 1 . The CS was the tarry smell of meta-cresol ( used as a stabilising vehicle in many insulin preparations and placebos ) . On day 2 , all participants received the CS and six administrations of placebo . Participants and experimenters were blinded to group assignment . Sixteen individuals were r and omised to and analysed in each group . Participants were sequentially numbered for group allocation . The main outcome measures were blood glucose and insulin , expressed as cumulative difference-from-baseline changes . Results While maintaining euglycaemia , intranasal insulin induced an increase of peripheral insulin on day 1 ( group 1 , 17.78 [ 21.88 ] pmol/l vs group 2 , −10.24 [ 9.42 ] pmol/l ) , and also on day  
    Output:
    
Animal and human studies were generally consistent in their findings ; however , the limited number of human studies makes it difficult to generalize and translate the results of animal research to humans .