SELECTIVE ATTENTION AND INSTRUMENTAL MODIFICATION OF THE GSR

A series of experiments were conducted on instrumental modification of the Galvanic Skin Response (GSR) in a discrimination procedure where preparatory signals indicated which discriminative stimulus was to occur. When shock avoidance was contingent upon the presence of a response the GSR was enhanced; when shock avoidance was contingent upon the inhibition of a response there was a decrement in reactivity. Heart rate acceleration occurred to Respond stimuli while deceleration occurred to Inhibit stimuli. Various types of cognitive strategies were reported by the subjects from attempts to control attention by attending less to stimuli associated with inhibition to attempts to arouse a response by thinking of exciting events and to inhibit by thinking of calming events. Postexperimental recognition of words tended to be negatively related to magnitude of response. When the verbal stimuli served directly as discriminative stimuli, however, these relationships tended to be reversed.     

Ultrastructural determinants of murine achilles tendon strength during healing

The mechanisms by which tendon strength is established during growth and development and restored following injury are not completely understood and are likely to be complex, multifactorial processes. Several studies examining the relationship between mechanical behavior and ultrastructural characteristics of tendons and ligaments during growth and maturation suggest that collagen fibril diameter is strongly correlated with tendon strength. Because of the similarities between development and repair processes of musculoskeletal tissues, increases in tendon strength during healing may be related to increases in fibril ultrastructural parameters such as fibril size, numerical density, and area fraction. In this study, we compared murine Achilles tendons at various time points after tenotomy with sham-operated controls in tensile tests to failure and examined tendons using electron microscopy to assess collagen fibril ultrastructure. We found that in the 6-week period following Achilles tenotomy, fibril mean diameter remained significantly smaller than sham-side diameter by a factor of 2-3. Despite the persistently small fibril size, increasing numerical density resulted in a gradual increase in fibril area fraction. Biomechanical strength did not reach that of intact tendons until some time between 5 and 7 weeks, approximately the same time period when fibril area fraction began to approach sham values. These data suggest that parameters other than collagen fibril size are most responsible for increased tendon strength during healing.     

Investigating Population Risk Factors of Pancreatic Cancer by Evaluation of Optical Markers in the Duodenal Mucosa

Pancreatic cancer screening has been hampered by the high rate of complications associated with interrogating the pancreas. The closest non-invasively accessible mucosa available for pancreatic cancer screening is the periampullary duodenal tissue. Our earlier report has shown the potential of using optical markers to interrogate this tissue for the presence of pancreatic cancer. In this study, we report a larger data set of low-coherence enhanced backscattering (LEBS) and elastic light scattering fingerprinting (ELF) optical markers from the periampullary duodenal mucosa. Optical measurements from biopsy samples were acquired from a total of 203 patients with varying clinical classification including healthy controls, a family history of pancreatic cancer, pancreatitis, mucinous cystic precursor lesions, pancreatic cancer, and other pancreatic malignancies. Evaluation of the performance of an independent testing set for discriminating healthy control patients from pancreatic cancer patients showed a 95% sensitivity, 71% specificity, and 85% area under the receiver operator characteristic (AUROC) curve. Importantly, this performance was uncompromised for detecting potentially curable stages of the disease. Additionally, optical markers in higher risk populations such as family history and pancreatitis had values between those of healthy control and pancreatic cancer patients, thus allowing for future investigations of screening from these high risk groups.     

Collegiate Athletic Trainers' Confidence in Helping Female Athletes With Eating Disorders

OBJECTIVE: To examine college athletic trainers' confidence in helping female athletes who have eating disorders. DESIGN AND SETTING: We mailed a 4-page, 53-item survey to head certified athletic trainers at all National Collegiate Athletic Association Division IA and IAA institutions (N = 236). A 2- wave mailing design was used to increase response rate. SUBJECTS: A total of 171 athletic trainers returned completed surveys for a response rate of 77%. Eleven institutions either did not identify their head athletic trainer or did not have an identifiable mailing address. Two surveys were undeliverable because of incorrect mailing addresses. MEASUREMENTS: The survey consisted of 4 subscales: (1) efficacy expectation, (2) outcome expectation, (3) outcome value, and (4) experience in dealing with eating disorders. Content validity was established by review from a national panel of experts. Reliability ranged from.66 to.73 for the subscales. RESULTS: Although virtually all athletic trainers (91%) had dealt with a female athlete with an eating disorder, only 1 in 4 (27%) felt confident identifying a female athlete with an eating disorder, and only 1 in 3 (38%) felt confident asking an athlete if she had an eating disorder. One in 4 athletic trainers (25%) worked at an institution that did not have a policy on handling eating disorders. Almost all athletic trainers (93%) felt that increased attention needs to be paid to preventing eating disorders among collegiate female athletes. CONCLUSIONS: Collegiate athletic programs are encouraged to develop and implement eating-disorder policies. Continuing education on the prevention of eating disorders among athletes is also strongly recommended.     

Engagement of gaze in capturing targets for future sequential manual actions

We investigated the role of saccadic gaze fixations in encoding target locations for planning a future manual task consisting of a sequence of discrete target-oriented actions. We hypothesized that fixations of the individual targets are necessary for accurate encoding of target locations and that there is a transfer of sequence information from visual encoding to manual recall. Subjects viewed four targets presented at random positions on a screen. After various delays following target extinction, the subjects marked the remembered target locations on the screen with the tip of a hand-held stick. When the targets were presented simultaneously among distracting elements, the overall accuracy of marking increased with presentation time and total number of targets fixated because the subjects had to serially fixate the individual targets to locate them. Without distractors, the marking accuracy was similarly high regardless of duration of target presentation (0.25-8 s) and number of targets fixated; it was comparable to that with distractors when all four targets had been fixated. This indicates parallel encoding of target locations largely based on peripheral vision. Location memory was stable in these tasks over the delay periods investigated (0.5-8 s). With parallel encoding there was a "shrinkage" in the visuomotor transformation, i.e., the distances between the markings were systematically smaller than the corresponding inter-target distances. When the targets were presented sequentially without distractors, marking accuracy improved with the total number of targets fixated and shrinkage in the visuomotor transformation occurred only with parallel encoding, i.e., when subjects did not fixate the targets. In all experimental conditions for trials in which targets were fixated during encoding, there was little correspondence between the marking sequence and the sequence in which the targets were fixated. We conclude that subjects benefit from fixating targets for subsequent target-oriented manual actions when the targets are presented among distractors and when presented sequentially; when distinct targets are presented simultaneously against a blank background, they are efficiently encoded in parallel largely by peripheral vision.     

Age-dependent effect of cholinergic lesion on dendritic morphology in rat frontal cortex

Previously, we demonstrated that plasticity of frontal cortex is altered in aging rats: 3 months after surgery, excitotoxic lesions of the nucleus basalis magnocellularis (NBM) produce larger declines in dendritic morphology in frontal cortex of aged rats relative to young adults. To determine whether the differential effect of the lesion was due specifically to loss of cholinergic input from the NBM, we assessed dendritic morphology in frontal cortex after specific cholinergic depletion in young adult, middle-aged, and aged male rats. Rats received unilateral sham or 192-IgG-saporin lesions of the NBM. Two weeks after surgery, brains were stained using a Golgi-Cox procedure. Dendritic morphology was quantified in pyramidal neurons in layers II-III of frontal cortex. Although lesions altered apical dendrites at all ages, these effects were most pronounced in aged rats. In addition, lesions produced marked atrophy of basilar dendrites in middle-aged and aged rats only. Thus, the differential dendritic atrophy resulting from NBM lesions in aged rats occurs within 2 weeks after lesion, and results specifically from loss of cholinergic innervation.     

Sociotropic cognition moderates stress-induced cardiovascular responsiveness in women through effects on total peripheral resistance, but not cardiac output.

Although cardiovascular disease (CVD) remains the leading cause of mortality in women, few studies have examined the role of psychosocial factors in its development. This study examined the moderating effects of sociotropic cognition (SC), a need for social acceptance and approval, on psychosocial stress-induced cardiovascular responsiveness (CVR) and affect reactivity in women. Sixty-eight normotensive, college-aged females were randomly assigned to a low or high social threat condition. Measures of systolic, diastolic and mean arterial blood pressures (SBP, DBP and MAP, respectively), heart rate (HR), cardiac output (CO), total peripheral resistance (TPR) and negative affect were collected during rest, and under conditions of high vs. low interpersonal threat. A two-step hierarchical regression analysis was performed to predict all response variables (BPs, HR, CO, TPR and affect). Increases in SBP, DBP, MAP, TPR and negative affect were greater in the high threat than low threat condition. Changes in SBP, MAP and TPR positively covaried with SC under conditions of high interpersonal threat, but showed no significant covariation in the low threat condition. The data suggest that an excessive need for social acceptance may contribute to rises in BP through an increase in TPR, but not CO under conditions of high social threat.     

Inhibition of arachidonic acid cyclo-oxygenase and lipoxygenase activities of leukocytes by indomethacin and compound BW755C

Arachidonic acid is metabolized via two pathways in leukocytes: cyclo-oxygenase, leading to the stable prostaglandins, and lipoxygenase, leading to hydroxyacids. Indomethacin inhibits the cyclo-oxygenase selectively, whereas compound BW755C (3-amino-1-(m-(trifluoromethyl)phenyl)-2-pyrazoline) inhibits both pathways equally. This offers a possible explanation for the differing activities of these two compounds in inflammatory models in vivo. The patterns of product inhibition by the two compounds support the suggestion that 11-HETE (hydroxy-eicosatetraenoic acid) and 15-HETE can arise by incomplete operation of the cyclo-oxygenase pathway.     

Benzodiazepine ligands,nociception and ‘defeat’ analgesia in male mice

Recent studies have indicated that defeat experience induces acute non-opioid analgesia in intruder mice. To investigate the potential involvement of benzodiazepine receptors in this biologically-relevant form of environmentally-induced antinociception, we initially assessed the effects of some benzodiazepine ligands on basal nociception (tail-flick assay). Chlordiazepoxide (5–30 mg/kg), midazolam (0.625–5 mg/kg), diazepam (0.5–4 mg/kg), Ro15-1788 (5–80 mg/kg) and CGS8216 (5 mg/kg) were found to be ineffective in altering basal nociception. However, higher doses of CGS8216 (10–20 mg/kg) induced significant analgesia, an effect also observed with the -carboline derivatives FG7142 (5–20 mg/kg) and DMCM (1–2 mg/kg). Time-course analyses revealed that the onset of CGS8216 analgesia was slower than for FG7142 and DMCM, but that all three drugs produced long-lasting elevations in tailflick latencies. The analgesic effects of FG7142 and DMCM were completely reversed by Ro15-1788 (20 mg/kg) and by chlordiazepoxide (20 mg/kg), suggesting mediation by benzodiazepine receptor mechanisms. Although CGS8216 analgesia was also reversed by Ro15-1788, it was unaffected by chlordiazepoxide; however, diazepam (5 mg/kg) did significantly attenuate the reaction. Further studies indicated that the antinociceptive consequences of defeat experience were dose-dependently blocked by Ro15-1788 (10–40 mg/kg) and by diazepam (0.5–2 mg/kg). Surprisingly, however, neither chlordiazepoxide (5–20 mg/kg) nor midazolam (1.25–2.5 mg/kg) blocked defeat analgesia under present test conditions. Although several issues remain unresolved, present findings would not be inconsistent with the proposal that stimuli associated with the acute stress of defeat experience release an endogenous ligand which acts in an inverse agonist-like manner at benzodiazepine sites.     

L-654,284 a new potent and selective α2-adrenoceptor antagonist

Summary L-654,284 ((2R, 12bS)-N-(1,3,4,6,7,12b-hexahydro-2H-benzo[b]-furo[2,3-a] quinolizine-2-yl)-N-methyl-2-hydroxyethanesulfonamide) was tested in several in vitro and in vivo models for ₂-adrenoceptor antagonist activity and compared to several reference agents. In vitro L-654,284 competed for the binding of ³H-clonidine or ³H-rauwolscine (K _i's 0.8 nM, 1.1 nM) and blocked the presynaptic effects of clonidine in the rat isolated vas deferens (pA₂, 9.1). L-654,284 exhibited marked ₂- vs. ₁-adrenoceptor selectivity in vitro, inhibiting ³H-prazosin binding with a K _i of 110 nM and blocking the effects of methoxamine on the vas deferens with a pA₂ of 7.5. In vivo L-654,284 at 22 nmoles/kg i.v. doubled the ED₅₀ of clonidine to produce mydriasis in rats. Given orally, the potency of L-654,284 in this test was reduced by a factor of 5.5. L-654,284 also potently increased cerebrocortical NE turnover in the rat, another in vivo index of ₂-adrenoceptor blockade in the central nervous system. In the periphery, L-654,284 demonstrated ₂-adrenoceptor selectivity by preferentially blocking the pressor effects of UK 14304 versus those of methoxamine in the pithed rat. Overall, L-654,284 was generally a more potent ₂-adrenoceptor antagonist than RX 781094 with comparable ₂/₁ selectivity and was several times more potent and ₂-selective than WY 26703 or yohimbine. In addition, L-654,284 had better (5–6 times) oral bioavailability than RX 781094 or WY 26703.