Social stress and glucocorticoids alter PERIOD2 rhythmicity in the liver, but not in the suprachiasmatic nucleus.

Circadian (~24 h) rhythms in behavior and physiological functions are under control of an endogenous circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN directly drives some of these rhythms or serves as a coordinator of peripheral oscillators residing in other tissues and organs. Disruption of the circadian organization may contribute to disease, including stress-related disorders. Previous research indicates that the master clock in the SCN is resistant to stress, although it is unclear whether stress affects rhythmicity in other tissues, possibly mediated by glucocorticoids, released in stressful situations. In the present study, we examined the effect of uncontrollable social defeat stress and glucocorticoid hormones on the central and peripheral clocks, respectively in the SCN and liver. Transgenic PERIOD2::LUCIFERASE knock-in mice were used to assess the rhythm of the clock protein PERIOD2 (PER2) in SCN slices and liver tissue collected after 10 consecutive days of social defeat stress. The rhythmicity of PER2 expression in the SCN was not affected by stress exposure, whereas in the liver the expression showed a delayed phase in defeated compared to non-defeated control mice. In a second experiment, brain slices and liver samples were collected from transgenic mice and exposed to different doses of corticosterone. Corticosterone did not affect PER2 rhythm of the SCN samples, but caused a phase shift in PER2 expression in liver samples. This study confirms earlier findings that the SCN is resistant to stress and shows that clocks in the liver are affected by social stress, which might be due to the direct influence of glucocorticoids released from the adrenal gland.

Integrated care pathways in the private sector.

ICPs are evidence- and outcome-based. The variances they expose can be analysed along with audit data. ICPs provide a useful audit tool, provided they are acted upon.

Comparing abilities of children with profound hearing impairments to learn consonants using electropalatography or traditional aural-oral techniques.

Two groups of nine children with profound hearing impairments and low intelligibility were taught to produce the consonants /t,d,k,g,s,z,S/ using either electropalatographic (palatometry) or traditional aural-oral techniques. Testing was completed pre-, immediately post-, and 6 months post-treatment by examining productions of CV syllables (V = /i,a/) using electropalatography-determined linguapalatal contacts and listener identifications. Intelligibility was also measured using the CID Picture Speech Intelligibility Evaluation (SPINE) test. Both groups improved their consonant productions as a result of 26 50-minute sessions. Sessions were given twice daily over 3- to 4-week training periods. Immediately post-treatment, the electropalatography-trained subjects produced better consonants as measured by linguapalatal contact patterns and listener identifications. The linguapalatal-contact patterns learned by the electropalatography-trained group better matched normal speaker productions than did those of the traditionally trained group. Both groups showed equal improvement for both post-treatment conditions when tested with the CID SPINE test. Although further research is needed, the results of this study suggest that electropalatographic techniques are, at least, equal alternatives to traditional aural-oral speech training techniques for speakers with profound hearing impairments.

Simultaneous derivation of clothing-specific heat exchange coefficients.

Clothing adds resistance to heat exchange between the wearer and the environment. If clothing-specific heat exchange coefficients are known, a combined rational/empirical approach can be used to describe thermal exchange between clothed humans and the environment. However, during exercise these coefficients--typically calculated using thermal manikins--change, primarily due to wetting of the fabric during intense sweating and body movement. A procedure is described that allows for the simultaneous determination of both total insulation (IT) and resistance to water vapor permeation (Re) on exercising clothed subjects without the need to directly measure skin water vapor pressure or continuously weigh the subjects. Two tests are performed by each subject in each clothing ensemble. In one test, ambient water vapor pressure (Pa) is systematically increased in stepwise fashion while dry-bulb temperature (Tdb) is held constant; in the second test protocol Pa is held constant while Tdb is increased. Heat exchange data are collected at the time at which core temperature is forced out of equilibrium by the environment (according to the assumption that heat production is balanced by heat loss immediately prior to this critical environmental limit). Previous studies using similar approaches have typically estimated IT a priori and used this value in the subsequent derivation of Re for each clothing ensemble or condition tested. In the proposed method, IT and Re are derived from the solution of two simultaneous equations based on heat balance data from both tests. This paper describes and critiques this methodology via an error analysis, and compares the coefficients obtained with those from similar trials using other physiological and nonphysiological approaches.

Comparing tongue positioning by normal-hearing and hearing-impaired children during vowel production.

Glossometric measures of tongue positions of 10 normal-hearing (NH) and 10 profoundly hearing-impaired (HI) children were compared during production of the eight vowels /i,I,E,ae,u,U,o,a/. The NH subjects used tongue positions with distinct vertical distances from the hard palate and discrete tongue shapes to distinguish the front vowels and the back vowels. The HI subjects produced vowels using a reduced vertical range and singular flat, high-back tongue shape. Token-to-token variability was greater for the HI subjects. Listener identifications of the vowels produced by the HI subjects fell in three categories: highly variable responses to /i/, low vowels for /I,E,ae,a/, and back vowels for /u,U,o/. The centralized, generally undifferentiated tongue positions and listener identifications for the HI subjects coincided with suppositions made from previous perceptual, acoustic, and physiologic findings.

Consonant lingual-palatal contacts produced by normal-hearing and hearing-impaired children.

Ten normal hearing (NH) and 18 profoundly hearing-impaired (HI) children were recorded using palatometry and audiotape while producing the consonants /t,d,k,g,s,z,integral of/ in CV syllables (V = /i, a/). The lingual-palatal contacts produced by the NH subjects for the alveolar stops were undifferentiated across voicing and vowel environment differences. Lingual-palatal contact patterns for the velar stops differed for vowel environment but not for voicing. The /s/ and /z/ sibilants were distinguished by groove width but not anterior place. Groove locations for /s/ and /z/ were more anterior than groove locations for /integral of/. The anterior grove location for the /integral of/ was vowel dependent. The HI subjects produced idiosyncratic lingual-palatal contact patterns. As patterns for individuals became more unique and less variable across the syllable stimuli, listener identifications showed correspondingly incorrect, undifferentiated responses. The atypical contact patterns used by the HI subjects often required interpretation of possible tongue activities during attempts at the various consonants.

Teaching consonants to profoundly hearing-impaired speakers using palatometry.

Five profoundly hearing-impaired children were taught the consonants /t,d,k,g,s,z integral of/ using palatometry. Changes in linguapalatal contact patterns and listener perceptions showed significant improvement in the place and manner of consonants produced by all subjects. Velar stops were as easily and accurately learned as alveolar stops. Distinctive sibilants were also found by the end of training. Sounds not previously present in a subject's phonetic repetoire were learned more accurately than those present but inaccurate prior to therapy. Voicing errors persisted. Two of the subjects showed evidence of newly established, unsolicited coarticulated movements. The results indicated that visual articulatory modeling and feedback of linguapalatal contact patterns is an effective means of teaching consonants and improving speech intelligibility.

Teaching vowels to profoundly hearing-impaired speakers using glossometry.

Glossometry was used to teach the four point vowels (/i,ae,u,a/) to 6 profoundly hearing-impaired children. Prior to treatment, all subjects evidenced centralized tongue positions during vowel productions. After 15 to 20 fifty-minute training sessions over 3- to 4-week time periods, all subjects showed greater diversification of tongue postures for the vowels, especially in tongue height. Listener identifications were generally better after therapy. The training results suggested that visually presented models and feedback of tongue positions can facilitate more appropriate tongue postures and improve vowel intelligibility by hearing-impaired speakers.

Predictors of clinical response in hirsute women treated with spironolactone.

OBJECTIVE: To examine the clinical efficacy of low dose spironolactone in hirsute women. DESIGN: Retrospective. SETTING: Outpatient endocrinology clinic. PATIENTS: One hundred nine consecutive women prescribed 75 to 100 mg/d spironolactone for at least 4 months in whom adequate follow-up data were available. RESULTS: Hirsutism improved in 72% of the women. Women with regular menses, whether or not they used oral contraceptives (OCs), had the highest response rate to spironolactone (78%), whereas women with irregular menses who did not use an OC had the lowest response rate (55%). Favorable responses were associated with increased severity of hirsutism (P = 0.04) and lower serum dehydroepiandrosterone sulfate levels (P = 0.05). Responders and nonresponders did not differ significantly in age (P = 0.10), duration of hirsutism (P = 0.14), pretreatment serum testosterone (T) (P = 0.48), or body mass index (P = 0.11). However, when each parameter was divided into subsets, trends toward decreasing response were observed with increasing age, duration of hirsutism over 15 years, and increasing serum T level. CONCLUSION: Low-dose spironolactone improves hirsutism in a majority of hirsute women, irrespective of age, severity or duration of hirsutism, menstrual status, or serum hormone levels.

Doing it right the first time. Interview by Wesley Curry.

Since 1979, Philip B. Crosby, Founder and Chairman of Philip Crosby Associates, Winter Park, Fla., has been applying the quality principles that he developed and applied at ITT for a variety of clients. About 900 firms, 200 of them in the Fortune 500, have gone through the process that he recommends for the development of a corporate attitude of quality. Earlier this year, Physician Executive interviewed Mr. Crosby. We talked about his general approach to issues of quality in products and services, and began to make the connection between his quality theories and their application in the health care industry.

Comparison of two-point discrimination testing devices.

In order to provide hand therapists and physicians with information regarding instruments for testing two-point discrimination we evaluated 20 noninjured and 18 nerve-injured patients using the three-prong Aesthesiometer, a paper clip, and a Disk-Criminator. Two-point discrimination was tested by means of a randomized order for the two different discrimination tests and the three different testing devices. The measurement for either moving or static two-point discrimination, when obtained with the three-prong Aesthesiometer, was consistently less sensitive than with the Disk-Criminator, and the correlation coefficient was the least between these two testing devices. The Disk-Criminator measurement had the smallest standard deviation among the three testing devices. In terms of desirability of the testing device tip geometry, translation of interprong distance to numerical rating scale, and facility of alternating between one- and two-prong testing techniques, the paper clip was judged to be the least favorable and the Disk-Criminator to be the most favorable test device.

Reliability of two-point discrimination measurements.

Both moving and static two-point discrimination are valid measurements of functional sensibility in the hand. The present study investigated the interobserver variability of these measurements when two observers used the same testing instrument and the same definition of the testing procedure's end point. In testing 30 nerve-injured patients, interobserver variability was found to vary within 1 mm, or less, for moving two-point discrimination in 93.3% of the measurements and for static two-point discrimination in 86.8% of the measurements. In only two of the 30 measurements of moving two-point discrimination and in four of the measurements for static two-point discrimination were interobserver differences equal to 2 mm. Measurements for both moving and static two-point discrimination were analyzed statistically by linear regression and correlation co-efficient techniques. The measurements for two-point discrimination obtained with the protocol employed in this study were found to have an interobserver reliability at the p less than 0.00001 level.