Changes to insulin sensitivity in glucose clearance systems and redox following dietary supplementation with a novel cysteine-rich protein: A pilot randomized controlled trial in humans with type-2 diabetes.

We recently developed a novel keratin-derived protein (KDP) rich in cysteine, glycine, and arginine, with the potential to alter tissue redox status and insulin sensitivity. The KDP was tested in 35 human adults with type-2 diabetes mellitus (T2DM) in a 14-wk randomised controlled pilot trial comprising three 2×20 g supplemental protein/day arms: KDP-whey (KDPWHE), whey (WHEY), non-protein isocaloric control (CON), with standardised exercise. Outcomes were measured morning fasted and following insulin-stimulation (80 mU/m2/min hyperinsulinaemic-isoglycaemic clamp). With KDPWHE supplementation there was good and very-good evidence for moderate-sized increases in insulin-stimulated glucose clearance rate (GCR; 26%; 90% confidence limits, CL 2%, 49%) and skeletal-muscle microvascular blood flow (46%; 16%, 83%), respectively, and good evidence for increased insulin-stimulated sarcoplasmic GLUT4 translocation (18%; 0%, 39%) vs CON. In contrast, WHEY did not effect GCR (-2%; -25%, 21%) and attenuated HbA1c lowering (14%; 5%, 24%) vs CON. KDPWHE effects on basal glutathione in erythrocytes and skeletal muscle were unclear, but in muscle there was very-good evidence for large increases in oxidised peroxiredoxin isoform 2 (oxiPRX2) (19%; 2.2%, 35%) and good evidence for lower GPx1 concentrations (-40%; -4.3%, -63%) vs CON; insulin stimulation, however, attenuated the basal oxiPRX2 response (4%; -16%, 24%), and increased GPx1 (39%; -5%, 101%) and SOD1 (26%; -3%, 60%) protein expression. Effects of KDPWHE on oxiPRX3 and NRF2 content, phosphorylation of capillary eNOS and insulin-signalling proteins upstream of GLUT4 translocation AktSer437 and AS160Thr642 were inconclusive, but there was good evidence for increased IRSSer312 (41%; 3%, 95%), insulin-stimulated NFκB-DNA binding (46%; 3.4%, 105%), and basal PAK-1Thr423/2Thr402 phosphorylation (143%; 66%, 257%) vs WHEY. Our findings provide good evidence to suggest that dietary supplementation with a novel edible keratin protein in humans with T2DM may increase glucose clearance and modify skeletal-muscle tissue redox and insulin sensitivity within systems involving peroxiredoxins, antioxidant expression, and glucose uptake.

Cortical processing to anorectal stimuli after rectal resection with and without radiotherapy.

BACKGROUND: Bowel dysfunction is common after surgery for rectal cancer, especially when neoadjuvant radiotherapy is used. The role of sensory function in the pathogenesis remains obscure, and the aim of the present study was to characterize the sensory pathways of the brain-gut axis in rectal cancer patients treated with resection ± radiotherapy compared with healthy volunteers. METHODS: Sensory evaluation by (neo)rectal distensions was performed and sensory evoked potentials (SEPs) were recorded during rapid balloon distensions of the (neo)rectum and anal canal in resected patients with (n = 8) or without (n = 12) radiotherapy. Twenty healthy volunteers were included for comparison. (Neo)rectal latencies and amplitudes of SEPs were compared and spectral band analysis from (neo)rectal and anal distensions was used as a proxy of neuronal processing. RESULTS: Neorectal sensation thresholds were significantly increased in both patient categories (all p < 0.008). There were no differences in (neo)rectal SEP latencies and amplitudes between groups. However, spectral analysis of (neo)rectal SEPs showed significant differences between all groups in all bands (all p < 0.01). On the other hand, anal SEP analyses only showed significant differences between the delta (0-4 Hz), theta (4-8 Hz) and, gamma 32-50 Hz) bands (all p < 0.02) between the subgroup of patients that also received radiotherapy and healthy volunteers. CONCLUSIONS: Surgery for rectal cancer leads to abnormal cortical processing of neorectal sensation. Additional radiotherapy leads to a different pattern of central sensory processing of neorectal and anal sensations. This may play a role in the functional outcome of these patients.

Behavioral testing and litter effects in the rabbit.

BACKGROUND: Behavioral testing provides an essential approach in further developing our understanding of brain structure and function. The aim of our study was to outline a more expanded approach to cognition- and anxiety-related behavior in the rabbit. METHODS: Twenty-one 70-day old rabbits (13 female, 8 male) were exposed to open field test, dark-light box test and object recognition testing with variations in inter-trial-interval, olfactory recognition and object location testing. Independent T-tests were used to compare data by individual baseline characteristics, i.e. birth weight, weight at testing, sex, litter #, litter size. RESULTS: In the open field test, median time spent in the center was 3.64 s (0.84-41.36) for the 9 rabbits who entered the center; median distance moved in the arena was 874.42 cm (54.20-3444.83). In the dark light box test, 12 rabbits entered the light compartment. In the object recognition task, rabbits spent significantly less time exploring the familiar object compared to the novel (0.40 s [0-2.8] vs. 3.17 s [1.30-32.69]; P = 0.003) when using a 30-min inter-trial interval, as well with a 90-min inter-trial interval: 0.87 s [0-7.8] vs. 7.65 s [0-37.6] (P = 0.008). However, recognition was lost when using a 24-h inter-trial interval (time spent exploring the familiar object: 3.33 [0-10.90]; novel object:3.87 [1.15-48.53]; n.s). In the object location task and in olfactory object recognition task, median discrimination indexes were 0.69 (-1 to 1) and 0.37 (-0.38 to 0.78) respectively, higher than level expected by chance (P < 0.001). Litter size >3 during the neonatal period was associated with increased explorative behavior in the dark light box test (P = 0.046) and in the visual object recognition task (P = 0.005), whereas body weight and sex were not. CONCLUSIONS: Settings and outcome measures for multiple behavioral tests, providing reference values and considerations for future developmental studies are reported. Discrimination and memory in the rabbit appear to relate to litter characteristics, although a larger sample size is needed to confirm our findings.

Cortical and spinal assessment - a comparative study using encephalography and the nociceptive withdrawal reflex.

BACKGROUND: Standardized objective methods to assess the analgesic effects of opioids, enable identification of underlying mechanisms of drug actions in the central nervous system. Opioids may exert their effect on both cortical and spinal levels. In this study actions of morphine at both levels were investigated, followed by analysis of a possible correlation between the cortical processing and spinal transmission. METHODS: The study was conducted after a double-blinded, two-way crossover design in thirty-nine healthy participants. Each participant received 30mg morphine or placebo as oral solution in randomized order. The electroencephalogram (EEG) was recorded during rest and during immersion of the hand into ice-water. Electrical stimulation of the sole of the foot was used to elicit the nociceptive withdrawal reflex and the reflex amplitude was recorded. RESULTS: Data from thirty subjects was included in the data analysis. There was no change in the activity in resting EEG (P>0.05) after morphine administration as compared to placebo. During cold pressor stimulation, morphine significantly lowered the relative activity in the delta (1-4Hz) band (P=0.03) and increased the activity in the alpha (8-12Hz) band (P=0.001) as compared to placebo. The reflex amplitudes significantly decreased after morphine administration (P=0.047) as compared to placebo. There was no correlation between individual EEG changes during cold pressor stimulation and the decrease in the reflex amplitude after morphine administration (P>0.05). CONCLUSIONS: Cold pressor EEG and the nociceptive reflex were more sensitive to morphine analgesia than resting EEG and can be used as standardized objective methods to assess opioid effects. However, no correlation between the analgesic effect of morphine on the spinal and cortical assessments could be demonstrated.

Prediction of postoperative opioid analgesia using clinical-experimental parameters and electroencephalography.

BACKGROUND: Opioids are often used for pain treatment, but the response is often insufficient and dependent on e.g. the pain condition, genetic factors and drug class. Thus, there is an urgent need to identify biomarkers to enable selection of the appropriate drug for the individual patient, a concept known as personalized medicine. Quantitative sensory testing (QST) and clinical parameters can provide some guidance for response, but better and more objective biomarkers are urgently warranted. Electroencephalography (EEG) may be suitable since it assesses the central nervous system where opioids mediate their effects. METHODS: Clinical parameters, QST and EEG (during rest and tonic pain) was recorded from patients the day prior to total hip replacement surgery. Postoperative pain treatment was performed using oxycodone and piritramide as patient-controlled analgesia. Patients were stratified into responders and non-responders based on pain ratings 24 h post-surgery. Parameters were analysed using conventional group-wise statistical methods. Furthermore, EEG was analysed by machine learning to predict individual response. RESULTS: Eighty-one patients were included, of which 51 responded to postoperative opioid treatment (30 non-responders). Conventional statistics showed that more severe pre-existing chronic pain was prevalent among non-responders to opioid treatment (p = 0.04). Preoperative EEG analysis was able to predict responders with an accuracy of 65% (p = 0.009), but only during tonic pain. CONCLUSIONS: Chronic pain grade before surgery is associated with the outcome of postoperative pain treatment. Furthermore, EEG shows potential as an objective biomarker and might be used to predict postoperative opioid analgesia. SIGNIFICANCE: The current clinical study demonstrates the viability of EEG as a biomarker and with results consistent with previous experimental results. The combined method of machine learning and electroencephalography offers promising results for future developments of personalized pain treatment.

Does Sacral Nerve Stimulation Improve Continence Through Enhanced Sensitivity of the Anal Canal? A Pilot Study.

BACKGROUND: It has been suggested that the effects of sacral nerve stimulation against fecal incontinence involve neuromodulation at spinal or supraspinal levels. OBJECTIVE: This study aims to investigate the afferent sensory pathways from the anorectum before and during sacral nerve stimulation. DESIGN: This is an explorative study. PATIENTS: Fifteen women with idiopathic fecal incontinence (mean age, 58 ± 12.2 years) were selected. INTERVENTIONS: Cortical evoked potentials were recorded during repeated rapid balloon distension of the rectum and the anal canal both before and during temporary sacral nerve stimulation. Stimuli applied were individualized according to the subjective urge to defecate. MAIN OUTCOME MEASURES: The main outcomes measured were 1) stimulus intensity, 2) latencies and amplitudes of cortical evoked potentials, and 3) spectral content in predefined frequency bands of cortical evoked potentials. RESULTS: The median Wexner fecal incontinence score improved from 15.5 ± 3.6 before to 6.7 ± 5 during sacral nerve stimulation (p < 0.001). Sacral nerve stimulation did not affect the threshold for urge to defecate during rectal distension (p = 0.64) but reduced the threshold from stimulation of the anal canal by 50% (p = 0.03). No statistically significant differences were found in latencies, amplitudes, or spectral analysis. LIMITATIONS: This is a pilot study of limited size. CONCLUSIONS: In patients with idiopathic fecal incontinence, sacral nerve stimulation reduced the threshold for urge to defecate elicited from the anal canal, whereas supraspinal responses remained unaltered. This may suggest that sacral nerve stimulation, at least in part, acts via somatic afferent fibers enhancing anal sensation.

The effect of age and unilateral leg immobilization for 2 weeks on substrate utilization during moderate-intensity exercise in human skeletal muscle.

KEY POINTS: This study aimed to provide molecular insight into the differential effects of age and physical inactivity on the regulation of substrate metabolism during moderate-intensity exercise. Using the arteriovenous balance technique, we studied the effect of immobilization of one leg for 2 weeks on leg substrate utilization in young and older men during two-legged dynamic knee-extensor moderate-intensity exercise, as well as changes in key proteins in muscle metabolism before and after exercise. Age and immobilization did not affect relative carbohydrate and fat utilization during exercise, but the older men had higher uptake of exogenous fatty acids, whereas the young men relied more on endogenous fatty acids during exercise. Using a combined whole-leg and molecular approach, we provide evidence that both age and physical inactivity result in intramuscular lipid accumulation, but this occurs only in part through the same mechanisms. ABSTRACT: Age and inactivity have been associated with intramuscular triglyceride (IMTG) accumulation. Here, we attempt to disentangle these factors by studying the effect of 2 weeks of unilateral leg immobilization on substrate utilization across the legs during moderate-intensity exercise in young (n = 17; 23 ± 1 years old) and older men (n = 15; 68 ± 1 years old), while the contralateral leg served as the control. After immobilization, the participants performed two-legged isolated knee-extensor exercise at 20 ± 1 W (∼50% maximal work capacity) for 45 min with catheters inserted in the brachial artery and both femoral veins. Biopsy samples obtained from vastus lateralis muscles of both legs before and after exercise were used for analysis of substrates, protein content and enzyme activities. During exercise, leg substrate utilization (respiratory quotient) did not differ between groups or legs. Leg fatty acid uptake was greater in older than in young men, and although young men demonstrated net leg glycerol release during exercise, older men showed net glycerol uptake. At baseline, IMTG, muscle pyruvate dehydrogenase complex activity and the protein content of adipose triglyceride lipase, acetyl-CoA carboxylase 2 and AMP-activated protein kinase (AMPK)γ3 were higher in young than in older men. Furthermore, adipose triglyceride lipase, plasma membrane-associated fatty acid binding protein and AMPKγ3 subunit protein contents were lower and IMTG was higher in the immobilized than the contralateral leg in young and older men. Thus, immobilization and age did not affect substrate choice (respiratory quotient) during moderate exercise, but the whole-leg and molecular differences in fatty acid mobilization could explain the age- and immobilization-induced IMTG accumulation.

Quantification and variability in colonic volume with a novel magnetic resonance imaging method.

BACKGROUND: Segmental distribution of colorectal volume is relevant in a number of diseases, but clinical and experimental use demands robust reliability and validity. Using a novel semi-automatic magnetic resonance imaging-based technique, the aims of this study were to describe: (i) inter-individual and intra-individual variability of segmental colorectal volumes between two observations in healthy subjects and (ii) the change in segmental colorectal volume distribution before and after defecation. METHODS: The inter-individual and intra-individual variability of four colorectal volumes (cecum/ascending colon, transverse, descending, and rectosigmoid colon) between two observations (separated by 52 ± 10) days was assessed in 25 healthy males and the effect of defecation on segmental colorectal volumes was studied in another seven healthy males. KEY RESULTS: No significant differences between the two observations were detected for any segments (All p > 0.05). Inter-individual variability varied across segments from low correlation in cecum/ascending colon (intra-class correlation coefficient [ICC] = 0.44) to moderate correlation in the descending colon (ICC = 0.61) and high correlation in the transverse (ICC = 0.78), rectosigmoid (ICC = 0.82), and total volume (ICC = 0.85). Overall intra-individual variability was low (coefficient of variance = 9%). After defecation the volume of the rectosigmoid decreased by 44% (p = 0.003). The change in rectosigmoid volume was associated with the true fecal volume (p = 0.02). CONCLUSIONS & INFERENCES: Imaging of segmental colorectal volume, morphology, and fecal accumulation is advantageous to conventional methods in its low variability, high spatial resolution, and its absence of contrast-enhancing agents and irradiation. Hence, the method is suitable for future clinical and interventional studies and for characterization of defecation physiology.

Machine learning on encephalographic activity may predict opioid analgesia.

BACKGROUND: Opioids are used for the treatment of pain. However, 30-50% of patients have insufficient effect to the opioid initially selected by the physician, and there is an urgent need for biomarkers to select responders to the most appropriate drug. Since opioids mediate their effect in the central nervous system, this study aimed to investigate if electroencephalography (EEG) during rest or pain before treatment could predict the analgesic response. METHODS: EEG from 62 channels was recorded in volunteers during rest and tonic pain (cold pressor test). Morphine (30 mg) or placebo was then administered, and the pain test repeated 60 min after. Washout period between drugs was 7 days. Based on pain ratings, subjects were stratified into responders and non-responders. Spectral analysis was performed on the EEG. Conventional statistics on group basis were used and, furthermore, the most discriminative EEG features were subjected to support vector machine classification to predict the response for the individual subjects. RESULTS: Conventional statistics on the frequency bands revealed no differences between responders and non-responders. On the individual basis, no differences between groups were found using resting EEG. However, EEG during cold pain was able to classify responders with an accuracy of 72% (p = 0.01) and the result was reproducible using baseline data from both study days. CONCLUSIONS: Machine learning based on EEG before treatment enabled separation between responders and non-responders. This study represents the first step towards the prediction of opioid analgesia based on EEG features prior to drug administration, and advocates for the use of machine learning in future studies.

Abnormal neuronal response to rectal and anal stimuli in patients with idiopathic fecal incontinence.

BACKGROUND: The pathophysiology behind idiopathic fecal incontinence (IFI) is poorly understood. We hypothesized abnormal sensory pathways along the brain-gut axis as a key player in this disease, reflected in cortical evoked potentials (CEP) from mechanical stimuli of the rectum and the anal canal. METHODS: CEPs were recorded during repeated rapid balloon distensions of the rectum and anal canal in 19 women with IFI (mean age: 60 ± 14, mean Wexner score: 14.7 ± 2.9) and in 19 healthy women (mean age: 56 ± 11, mean Wexner score: 1.1 ± 1.3). Latencies, amplitudes and topography of CEPs elicited by rectal distension were compared between the groups. CEPs from both rectal and anal distensions were examined using spectral band analysis of single sweeps determining the relative amplitude of five spectral bands as a proxy of neuronal processing. KEY RESULTS: Compared to controls IFI patients had prolonged latency of CEPs from rectal distension by up to 27% (p < 0.001) while amplitudes and topography were similar (all p > 0.7 and all p > 0.23). Spectral analysis of CEPs from rectal distensions showed no difference (all p > 0.1) between groups. However, analysis of CEPs following distension of the anal canal resulted in abnormally low activity in beta (8-12 Hz; p < 0.001) band and high activity in the gamma (32-70 Hz; p = 0.04) band in patients. CONCLUSIONS & INFERENCES: IFI seems to be associated with impaired ano-rectal sensory functions in both the afferent fibers to the brain and the cortical processing of anal sensory pathways. This may play a central role for the pathogenesis of IFI.

Dynamic spectral indices of the electroencephalogram provide new insights into tonic pain.

OBJECTIVE: This study aimed to investigate reliability of electroencephalography (EEG) during rest and tonic pain. Furthermore, changes in EEG between the two states as well as dynamics and relation to pain ratings were investigated. METHODS: On two separate days EEG was recorded in 39 subjects during rest and tonic pain (cold pressor test: left hand held in 2°C water for 2 min.) while pain intensity was rated continuously. Dynamic spectral analysis was performed on the EEG. Between-day reliability of spectral indices was assessed and correlations to pain ratings were investigated. RESULTS: EEG reliability was high during both states. The relative spectral indices increased in delta (1-4 Hz; P=0.0002), beta3 (18-32 Hz; P<0.0001) and gamma (32-70 Hz; P<0.0001) bands during tonic pain, and decreased in theta (4-8 Hz; P<0.0001), alpha1 (8-10 Hz; P<0.0001), alpha2 (10-12 Hz; P<0.0001) bands. Theta, beta3 and gamma bands correlated significantly to the area-under-curve of pain ratings, but only theta was dynamic and correlated to the pain ratings (R=0.88, P<0.0001). CONCLUSIONS: EEG assessed during tonic pain is a valid experimental pain model both in terms of reliability between days and in connection between cortical activity and pain perception. SIGNIFICANCE: EEG during tonic pain is more pain-specific and should be used in future basic and pharmacological studies.

Cortical evoked potentials in response to rapid balloon distension of the rectum and anal canal.

BACKGROUND: Neurophysiological evaluation of anorectal sensory function is hampered by a paucity of methods. Rapid balloon distension (RBD) has been introduced to describe the cerebral response to rectal distension, but it has not successfully been applied to the anal canal. METHODS: Nineteen healthy women received 30 RBDs in the rectum and the anal canal at intensities corresponding to sensory and unpleasantness thresholds, and response was recorded as cortical evoked potentials (CEPs) in 64-channels. The anal canal stimulations at unpleasantness level were repeated after 4 min to test the within-day reproducibility. CEPs were averaged, and to overcome latency variation related to jitter the spectral content of single sweeps was also computed. KEY RESULTS: Repeated stimulation of the anal canal generated CEPs with similar latencies but smaller amplitudes compared to those from the rectum. Due to latency jitter, reproducibility of averaged CEPs was lower than what was found in the rectum. The most reproducible feature was N2P2 peak-to-peak amplitude with intra-class correlation coefficient (ICC) of 0.7 and coefficient of variation (CV) of 18%. Spectral content of the single sweeps showed reproducibility with ICCs for all bands >0.8 and corresponding CVs <7%. CONCLUSIONS & INFERENCES: Cortical potentials evoked from the anal canal are challenged by latency jitter likely related to variability in muscle tone due to the distensions. Using single-sweep analysis, anal CEPs proved to be reproducible and should be used in future evaluation of the anal function.

The cysteine 34 residue of A1M/α1-microglobulin is essential for protection of irradiated cell cultures and reduction of carbonyl groups.

α1-microglobulin (A1M) is a 26 kDa plasma and a tissue protein belonging to the lipocalin family. The reductase and free radical scavenger A1M has been shown to protect cells and extracellular matrix against oxidative and irradiation-induced damage. The reductase activity was previously shown to depend upon an unpaired cysteinyl side-chain, C34, and three lysyl side-chains, K92, 118, and 130, located around the open end of the lipocalin pocket. The aim of this work was to investigate whether the cell and matrix protection by A1M is a result of its reductase activity by using A1M-variants with site-directed mutations of the C34, K92, K118, and K130 positions. The results show that the C34 side-chain is an absolute requirement for protection of HepG2 cell cultures against alpha-particle irradiation-induced cell death, upregulation of stress response and cell cycle regulation genes. Mutation of C34 also resulted in loss of the reduction capacity toward heme- and hydrogen peroxide-oxidized collagen, and the radical species 2,2´-azino-bis (3-ethyl-benzo-thiazoline-6-sulphonic acid) (ABTS). Furthermore, mutation of C34 significantly suppressed the cell-uptake of A1M. The K92, K118, and K130 side-chains were of minor importance in cell protection and reduction of oxidized collagen but strongly influenced the reduction of the ABTS-radical. It is concluded that antioxidative protection of cells and collagen by A1M is totally dependent on its C34 amino acid residue. A model of the cell protection mechanism of A1M should be based on the redox activity of the free thiolyl group of the C34 side-chain and a regulatory role of the K92, K118, and K130 residues.

The spinal curve in standing and sitting postures in children with idiopathic scoliosis.

STUDY DESIGN: A sample of convenience of children with moderate idiopathic scoliosis without bracing or surgery was studied. The sample consisted of 19 children, aged 9 to 16 years, with mean Cobb angle of 24 degrees. The spinal configurations and paraspinal muscle activity in several commonly assumed postures were examined. OBJECTIVES: To determine how the apex angles, verticality of spine, and muscle activity vary with the assumed posture and whether the location and the number of spinal curves affect these variables. SUMMARY OF BACKGROUND DATA: It has been suggested that the configuration of the spine in commonly assumed postures can affect the spinal curve in scoliosis because of gravitational bending moments. There is, however, a paucity of data obtained in subjects in sitting postures that school-age children assume daily for prolonged periods. Absence of bilateral symmetry in pressure during sitting has been described, but its effect on the spinal apex angle has not been investigated. METHODS: Infrared-emitting markers, whose three-dimensional positions could be tracked by a pair of cameras, were affixed to the spine. The natural postures studied were relaxed standing, relaxed sitting, erect sitting, and writing while seated. Electromyographic activity in muscles close to the spinal apexes was recorded bilaterally for each test posture. RESULTS: Subjects leaned laterally and, in general, anteriorly, in all test postures, rather than placing the C7 vertebra vertically above S1. The direction of lean and the change in the spinal apex angle from standing to sitting varied depending on whether the spinal curve was single or double, thoracic or lumbar. Subjects with single curves, whether thoracic or lumbar, tended to lean laterally toward the convexity of their curve apex--that is, the lean was in a direction that reduced the apex angle. Subjects with double curves (thoracic and lumbar), in all postures except relaxed sitting, tended to lean toward the convexity of the lumbar curve, thereby reducing the lumbar apex angle and exacerbating the thoracic angle. Most subjects' apex angles were smaller in relaxed or erect sitting than in relaxed standing. Electromyographic activity was in general greater on the convex side of the curve, with greatest activity in erect sitting. CONCLUSIONS: The findings indicate that in self-selected postures the gravitational effect of leaning and the muscle activity in paraspinal muscles may serve to reduce the apex angle. Thus, a fully upright, centered posture may not be best for correction of every patient's spinal curve.

The resurgence of tuberculosis: risk in health care settings.

After many years of steady decline in reported cases, TB is resurging in the U.S. as a clinical problem and a public health problem. TB continues to be an occupational hazard for health care workers and others in work environments where spaces are enclosed, ventilation is poor, and personnel are crowded. Transmission occurs by inhaling droplet nuclei generated by persons with active TB. Education, active surveillance, reporting, and an expanded role in community action are appropriate roles for the occupational health nurse.

A member of the steroid hormone receptor gene family is expressed in the 20-OH-ecdysone inducible puff 75B in Drosophila melanogaster.

Drosophila melanogaster DNA has been cloned which encompasses a major part of the 20-OH-ecdysone inducible puff 75B. One 20-OH-ecdysone responsive transcription unit was detected which is expressed into two transcripts which accumulate upon the incubation of salivary glands of 3rd instar larvae with 20-OH-ecdysone. This accumulation is correlated with the 20-OH-ecdysone induced activity of puff 75B. 75B cDNA analysis indicates that the activity of puff 75B leads to the synthesis of a protein which belongs to the steroid and thyroid hormone receptor superfamily. The highest similarity of the derived 75B protein sequence was found to the DNA and ligand binding domains of human retinoic acid receptor. A study of the tissue distribution in larvae revealed that 75B mRNA is present in most, if not all 20-OH-ecdysone target tissues. It is proposed that 75B protein is a DNA-binding protein playing a key role in mediating the regulation of the larval molt by 20-OH-ecdysone.

Parapodium redesigned for sitting.

Clinical experience with the Toronto parapodium demonstrates it to have valuable functional use. Young children wearing the orthosis, however, do not participate in group activities requiring unaided sitting and standing. We have redesigned the hip and knee locks to make these maneuvers easier. This modification has allowed the young child to sit and stand without assistance and to develop greater confidence and independence at home and in the classroom.

The retention of calcium, iron, phosphorus, and magnesium during pregnancy: the adequacy of prenatal diets with and without supplementation.

Vitamin and mineral supplementation is often prescribed by physicians to meet the additional nutrient requirements of pregnancy. In order to partially ascertain the effectiveness of these prenatal supplements, the retention of calcium and iron was determined in pregnant women consuming supplemented or unsupplemented self-selected diets. The retention of phosphorus and magnesium, minerals not included in the prenatal supplements, was also determined. Seven-day metabolic balance experiments spaced periodically throughout the pregnancy were conducted on 10 healthy pregnant white women. The retention of calcium by the supplemented group was comparable to that of the unsupplemented group, while the retention of iron was more dependent on the magnitude of the iron intake than on its source. Although no supplement contained phosphate, the intake of phosphorus met the recommended allowances for this mineral. Significantly related to the intake of dietary calcium, the adequate phosphorus intakes reflected diets providing adequate calcium. The mean magnesium intake was only 60% of the recently established recommended dietary allowance. Although the calcium and iron salts provided by the prenatal supplements were well utilized, the intakes of phosphorus and magnesium indicate that the reliance on the effectiveness of mineral supplements should not lessen the emphasis by the physician on the importance of a good prenatal diet.

An audio-tutorial aid for dietary instruction in renal dialysis.

Four 10-min, color, video-tape cassettes, which include graphics, cartoon characters with dialogue, and live demonstrations, were developed to improve dietary adherence by patients receiving maintenance hemodialysis. The format of the tapes was directed primarily to the needs of educationally deprived patients. The tapes were assessed for efficacy following presentation to sixteen randomly selected patients in he University of Tennessee Artificial Kidney Center, Memphis. Highly significant, positive changes were revealed when post-test informational scores were compared with pre-test scores. In the behavioral scores, some positive changes were observed, although further reinforcement would be needed to achieve sufficient application of the information.