Comparison between continued inpatient treatment versus day patient treatment after short inpatient care in early onset anorexia nervosa (COTIDEA trial): a study protocol for a non-inferiority randomised controlled trial.

BACKGROUND: In children with early-onset anorexia nervosa (first symptoms before 13 years old, EO-AN), experts recommend initial outpatient treatment but in-patient treatment (IP) is frequently indicated due to acute medical instability or for those who have not improved with outpatient treatment. This IP can target either a partial weight restauration or a total weight normalization (return to the previous BMI growth trajectory). There are no evidence in the literature on which is the better therapeutic option in EOAN. But as long length of stay induce social isolation, with elevated costs, we wonder if a stepped-care model of daypatient treatment (DP) after short IP stabilisation may be a treatment option as effective as full-time IP to target weight normalization. We designed a two-arm randomised controlled trial testing the non-inferiority of a stepped-care model of DP after short IP stabilisation versus full-time IP. METHODS: Eighty-eight children aged 8 to 13 years suffering from EOAN with initial severe undernutrition will be randomly allocated to either IP treatment as usual or a stepped care DP model both targeting weight normalization. Assessments will be conducted at inclusion, somatic stabilization, weight normalization, 6 months and 12 months post randomisation. The primary outcome will be BMI at 12 months post-randomisation. Secondaries outcomes will included clinical (tanner stage), biological (prealbumin, leptin, total ghrelin and IGF1) and radiological (bone mineralization and maturation) outcomes, eating symptomatology and psychiatric assessments, motivation to change, treatment acceptability and quality of life assessments, cost-utility and cost-effectiveness analyses. DISCUSSION: COTIDEA will provide rigorous evaluation of treatment alternative to full-time inpatient treatment to allow a reduction of social iatrogenic link to hospital length of stay and associated costs. TRIAL REGISTRATION: Trial is registered on ClinicalTrials.gov (NCT04479683).

Obesity prevention in English primary schools: headteacher perspectives.

Schools are seen as important contributors to obesity prevention, yet face barriers in fulfilling this function. This qualitative study investigates headteacher views on the primary school role in preventing obesity. Semi-structured interviews were held with 22 headteachers from ethnically and socio-economically diverse schools in the West Midlands, UK. Data analysis was conducted using the framework approach. Two over-arching categories were identified: 'School roles and responsibilities' and 'Influencing factors'. Participants agreed that although schools contribute towards obesity prevention in many ways, a moral responsibility to support children's holistic development was the principal motivator, rather than preventing obesity per se. The perceived impact on learning was a key driver for promoting health. Parents were believed to have the main responsibility for preventing obesity, but barriers were identified. Whilst headteachers recognized the advantageous position of schools in offering support to parents, opinion varied on the degree to which schools could and should take on this role. Headteachers serving more deprived areas reported adopting certain responsibilities that elsewhere were fulfilled by parents, and were more likely to view working with families on healthy lifestyles as an important school function. Several factors were perceived as barriers to schools doing more to prevent obesity, including academic pressure, access to expert support and space. In conclusion, school leaders need more support, through resources and government policy, to enable them to maximize their role in obesity prevention. Additionally, school-based obesity prevention should be an integral part of the education agenda rather than bolt-on initiatives.

Higher reward value of starvation imagery in anorexia nervosa and association with the Val66Met BDNF polymorphism.

Recent studies support the idea that abnormalities of the reward system contribute to onset and maintenance of anorexia nervosa (AN). Next to cues coding for overweight, other research suggest cues triggering the proposed starvation dependence to be pivotally involved in the AN pathogenesis. We assessed the characteristics of the cognitive, emotional and physiologic response toward disease-specific pictures of female body shapes, in adult AN patients compared with healthy control (HC) women. Frequency and amplitude of skin conductance response (SCR) in 71 patients with AN and 20 HC were registered during processing of stimuli of three weight categories (over-, under- and normal weight). We then assessed the role of the Val66Met BDNF polymorphism as a potential intermediate factor. AN patients reported more positive feelings during processing of underweight stimuli and more negative feelings for normal- and overweight stimuli. The SCR showed a group effect (P=0.007), AN patients showing overall higher frequency of the response. SCR within patients was more frequent during processing of underweight stimuli compared with normal- and overweight stimuli. The Met allele of the BDNF gene was not more frequent in patients compared with controls, but was associated to an increased frequency of SCR (P=0.008) in response to cues for starvation. A higher positive value of starvation, rather than more negative one of overweight, might more accurately define females with AN. The Met allele of the BDNF gene could partly mediate the higher reward value of starvation observed in AN.

Experience with the treatment of argininosuccinic aciduria during pregnancy.

We present the details of the management and the outcome of a pregnancy of a woman affected with argininosuccinic aciduria. Management with a closely monitored, protein-restricted diet, supplemented with L-arginine, resulted in the birth of a healthy infant boy and an uneventful perinatal course for the mother.

Allelic variation at Psy1-A1 and association with yellow pigment in durum wheat grain.

The yellow pigment (YP) of durum wheat (Triticum turgidum L. var durum) semolina is due in part to the presence of carotenoid pigments found in the endosperm and is an important end-use quality trait. Phytoene synthase (Psy) is considered a rate-limiting enzyme in the carotenoid biosynthetic pathway and in this study, three alleles of Psy1-A1 were sequenced from four durum wheat cultivars and a co-dominant marker was developed for genetic mapping. Psy1-A1 mapped to chromosome 7AL near Xwmc809 in three durum mapping populations and was significantly associated with a pigment quantitative trait loci (QTL) identified on that chromosome. A second QTL localized 25 cM proximal to Psy1-A1 in two populations, and the interaction between the two QTL was not significant. Consistent with QTL mapping data, the Psy1-A1o allele was associated with elevated pigment in a validation population comprising 93 diverse cultivars and breeding lines. These results confirm an earlier hypothesis that Psy1, and at least one additional gene in the distal region of 7AL, are associated with grain YP differences in durum wheat. The functional co-dominant marker developed in this study differentiates the Psy1-A1 alleles reported here and could be used as a target to enhance YP selection in durum wheat breeding programs.

An endoscopically implantable device stimulates the lower esophageal sphincter on demand by remote control: a study using a canine model.

BACKGROUND AND STUDY AIMS: Implantable microstimulators (IMS) have been used in a variety of medical conditions. Selective stimulation to increase lower esophageal sphincter (LES) pressure may be useful in the control of gastroesophageal reflux disease. We evaluated on-demand stimulation of the LES with an endoscopically implanted microstimulator. MATERIALS AND METHODS: We performed acute experiments in three 30-kg dogs. After LES manometry, a 3.3 mm x 28 mm microstimulator (the Bion) was implanted into the LES. Manometry was repeated with and without IMS stimulation to record the changes in LES pressure. Stimulation amplitude was varied from 3 mA to 10 mA, with a fixed frequency of 20 Hz and a pulse width of 200 microsec. RESULTS: The mean LES pressures prior to IMS implantation in the three dogs were 13.0 mm Hg, 5.0 mm Hg, and 14.9 mm Hg. The mean pressures were not significantly changed by IMS placement. There were no documented changes in LES pressure when the amplitude of stimulation was less than 8 mA. After stimulation of the IMS at a setting of 10 mA in dogs 1 and 2 and at 8mA in dog 3, however, the resultant LES pressures were 62.1 mm Hg, 35.1 mm Hg, and 26.8 mm Hg respectively, more than three times higher than post-implantation baseline levels (P < 0.02). CONCLUSIONS: The LES pressure can be increased using an on-demand microstimulator. The implantation procedure is minimally invasive, represents a novel therapeutic approach to gastroesophageal reflux disease, and may have therapeutic potential for other gastrointestinal motility disorders.

Is blood the ideal submucosal cushioning agent? A comparative study in a porcine model.

BACKGROUND AND STUDY AIMS: Creation of a submucosal cushion before endoscopic mucosal resection (EMR) significantly reduces perforation risk. We evaluated six solutions as cushioning agents in live pigs. MATERIAL AND METHODS: 5 ml of normal saline, normal saline plus epinephrine, albumin 12.5 %, albumin 25 %, hydroxypropyl methylcellulose, and the pig's own whole blood were endoscopically injected into the porcine esophageal submucosa. Blood was obtained from a peripheral vein immediately before injection. Injections were made every 4 cm from the gastroesophageal junction. The time from completion of the injection to disappearance of the cushion was recorded. Endoscopy was repeated at 48 hours post injection. Two EMRs were performed after blood injection. Statistical analysis employed one-way analysis of variance followed by pairwise T test comparisons using the Bonferroni correction. RESULTS: Five animal experiments were completed. The mean time to dissipation of the submucosal cushion was shortest for saline plus epinephrine sites (2.87 minutes, SD 2.21) followed by the saline (4.8 minutes, SD 1.56), albumin 12.5 % (5.68 minutes, SD 3.48), albumin 25 % (7.83 minutes, SD 2.02), hydroxypropyl methylcellulose (9.77 minutes, SD 1.55), and blood sites (38.6 minutes, SD 6.07). Injection of blood resulted in significantly longer mucosal elevation than any other solution ( P < 0.0007). Blood from the cushion did not hamper visualization and facilitated EMR. CONCLUSION: Blood produces the most durable cushion compared with standard agents, also having the advantages of being readily available and without cost. Albumin 25 % provides as durable a cushion as hydroxypropyl methylcellulose.

Are HIV/AIDS services in Leeds, UK, able to meet the needs of asylum seekers?

BACKGROUND: The Yorkshire and Humberside region of England ranks second only to London for reception of those seeking asylum in the UK. Human immunodeficiency virus (HIV) prevalence amongst asylum seekers is likely to mirror that in the country of origin. In 2001, the city of Leeds received 1100 asylum seekers, including dependents. Many of these were from areas with high seroprevalence of HIV, and HIV-infected asylum seekers require medical and social support. Are the current services for HIV-infected persons in Leeds appropriate and adequate for this new patient group? Provision of sexual health services for this client group needs to be evaluated. OBJECTIVES: To determine whether existing HIV/acquired immunodeficiency syndrome (AIDS) services in Leeds meet the needs of HIV-positive asylum seekers. METHODS: This was a qualitative study using semi-structured interviews. Seven service providers and 14 HIV-positive patients at Leeds Centre for Sexual Health, six of whom were asylum seekers, took part in the study. RESULTS: Asylum seekers and UK residents were equally satisfied with HIV/AIDS services at Leeds Centre for Sexual Health. Other agencies such as the Health Access Team and Terrence Higgins Trust had different strengths that provided valuable support for this client group. Unmet needs of asylum seekers were identified, such as specialist services for torture victims and educational opportunities. In areas of asylum seeker dispersal with increased case loads, this methodology may inform development of client-centred care networks.

The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects.

RATIONALE: Extracts of Bacopa monniera have been reported to exert cognitive enhancing effects in animals. However, the effects on human cognition are inconclusive. OBJECTIVE: The current study examined the chronic effects of an extract of B. monniera (Keenmind) on cognitive function in healthy human subjects. METHODS: The study was a double-blind placebo-controlled independent-group design in which subjects were randomly allocated to one of two treatment conditions, B. monniera (300 mg) or placebo. Neuropsychological testing was conducted pre-(baseline) and at 5 and 12 weeks post drug administration. RESULTS: B. monniera significantly improved speed of visual information processing measured by the IT task, learning rate and memory consolidation measured by the AVLT (P<0.05), and state anxiety (P<0.001) compared to placebo, with maximal effects evident after 12 weeks. CONCLUSIONS: These findings suggest that B. monniera may improve higher order cognitive processes that are critically dependent on the input of information from our environment such as learning and memory.

Neuropsychological changes after 30-day Ginkgo biloba administration in healthy participants.

Ginkgo biloba extract (EGb) from the world's oldest living tree has been reputed to ameliorate cognitive decline in the elderly and slow cognitive deterioration in patients with dementia of the Alzheimer's type. EGb remains as one of the most popular plant extracts to alleviate symptoms associated with a range of cognitive disorders such as Alzheimer's disease, vascular dementia and age-related amnesic conditions. EGb is known to contain a range of chemically active components that have antagonistic effects on platelet-activating factor, free-radical scavenging activity and direct effects on the cholinergic neurotransmitter system. Recently there has been much speculation, that EGb may act as a 'smart drug' or nootropic agent in the healthy young to improve intelligence. We conducted a 30-d randomized, double-blind, placebo-controlled clinical trial in which 61 participants were administered a battery of validated neuropsychological tests before and after treatment. Statistical analysis indicated significant improvements in speed of information processing working memory and executive processing attributable to the EGb.

Chiropractors and return-to-work: the experiences of three Canadian focus groups.

OBJECTIVES: To explore the views of chiropractors about timely return-to-work in treating patients with musculoskeletal injuries, to identify the approaches used by chiropractors when treating injured workers with musculoskeletal disorders, and to learn about chiropractors' perspectives on the barriers and facilitators of successful return-to-work. DESIGN: Qualitative study of 3 focus groups of chiropractors. METHODS: Focus groups of 8 to 11 chiropractors were conducted in 3 large Canadian cities. The selected participants were experienced in treating patients with occupational musculoskeletal injuries. Standard questions were used to collect data. The data from each focus group were coded and analyzed separately and then considered in relation to each other. RESULTS: The participants indicated that timely return-to-work depends on patients' characteristics, severity of injury, clinical progress, the availability of work accommodation, and clinical judgment. The chiropractors commented that their treatment of injured workers rests on their strength in diagnosis and treatment and on providing patient-centered care. Positive human relations within workplaces and the ability to accommodate the work of an injured worker were described as important in return-to-work programs. The participants believed that a bias against chiropractic is present within the medical profession and workers' compensation boards. They viewed this bias as an important barrier when assisting their patients to successfully return to work. CONCLUSION: The broad approaches described by the participating chiropractors to return injured workers to work are consistent with those proposed in evidence-based practice guidelines. Better communication among chiropractors, medical doctors, and workers' compensation boards would likely decrease interprofessional tensions and improve the recovery of workers with musculoskeletal injuries.

The acute effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy normal subjects.

The Ayurvedic medicine Bacopa monniera (Brahmi) has been shown to exert cognitive enhancing effects in animals. The current study examined the acute effects of an extract of Bacopa monniera on cognitive function in normal healthy human subjects. The study was a double-blind, placebo-controlled independent group design in which subjects were randomly allocated to one of two treatment conditions, Bacopa monniera (300 mg) (n = 18) or placebo (n = 20). Neuropsychological testing was conducted before and 2 h after drug administration. No significant changes were found on any of the tests. The findings suggest that Bacopa monniera, at least for the dose administered, has no acute effects on cognitive functioning in normal healthy subjects. Copyright 2001 John Wiley & Sons, Ltd.

Analysis of a clinical sign in traditional Chinese medicine using Doppler ultrasound.

Using Doppler ultrasound, a study was done on the characteristics of the radial pulse at the wrist in pregnant and non-pregnant women in order to test the hypothesis that the traditional Chinese medicine 'smooth pulse' of pregnancy has a physiological basis. Comparison of pulse characteristics in a small series of subjects strongly supports this hypothesis.

Cardiovascular responses to an orthostatic challenge and electrical-stimulation-induced leg muscle contractions in individuals with paraplegia.

The purpose of this study was to investigate the cardiovascular and haemodynamic responses that occur during moderate orthostatic challenge in people with paraplegia, and the effect of electrical stimulation (ES)-induced leg muscle contractions on their responses to orthostatic challenge. Eight males with complete spinal lesions between the 5th and 12th thoracic vertebrae (PARA) and eight able-bodied individuals (AB) volunteered for this study. Changes in heart rate (fc), stroke volume (SV), cardiac output (Qc), mean arterial pressure (MAP), total peripheral resistance (TPR), limb volumes and indices of neural modulation of fc, [parasympathetic (PNS) and sympathetic (SNS) nervous system indicators] were assessed during: (1) supine rest (REST), (2) REST with lower-body negative pressure at -30 torr (LBNP -30, where 1 torr = 133.32 N/m2), and (3) for PARA only, LBNP -30 with ES-induced leg muscle contractions (LBNP + ES). LBNP -30 elicited a decrease in SV (by 23% and 22%), Qc (by 15% and 18%) and the PNS indicator, but an increase in fc (by 10% and 9%), TPR (by 23% and 17%) and calf volume (by 1.51% and 4.04%) in both PARA and AB subjects, respectively. The SNS indicator was increased in the AB group only. Compared to LBNP -30, LBNP + ES increased SV (by 20%) and Qc (by 16%), and decreased TPR (by 12%) in the PARA group. MAP was unchanged from REST during all trials, for both groups. The orthostatic challenge induced by LBNP -30 elicited similar cardiovascular adaptations in PARA and AB subjects. ES-induced muscle contractions during LBNP -30 augmented the cardiovascular responses exhibited by the PARA group, probably via reactivation of the skeletal muscle pump and improved venous return.

SQUID detected NMR and NQR. Superconducting Quantum Interference Device.

The dc Superconducting QUantum Interference Device (SQUID) is a sensitive detector of magnetic flux, with a typical flux noise of the order 1 muphi0 Hz(-1/2) at liquid helium temperatures. Here phi0 = h/2e is the flux quantum. In our NMR or NQR spectrometer, a niobium wire coil wrapped around the sample is coupled to a thin film superconducting coil deposited on the SQUID to form a flux transformer. With this untuned input circuit the SQUID measures the flux, rather than the rate of change of flux, and thus retains its high sensitivity down to arbitrarily low frequencies. This feature is exploited in a cw spectrometer that monitors the change in the static magnetization of a sample induced by radio frequency irradiation. Examples of this technique are the detection of NQR in 27Al in sapphire and 11B in boron nitride, and a level crossing technique to enhance the signal of 14N in peptides. Research is now focused on a SQUID-based spectrometer for pulsed NQR and NMR, which has a bandwidth of 0-5 MHz. This spectrometer is used with spin-echo techniques to measure the NQR longitudinal and transverse relaxation times of 14N in NH4ClO4, 63+/-6 ms and 22+/-2 ms, respectively. With the aid of two-frequency pulses to excite the 359 kHz and 714 kHz resonances in ruby simultaneously, it is possible to obtain a two-dimensional NQR spectrum. As a third example, the pulsed spectrometer is used to study NMR spectrum of 129Xe after polariza-tion with optically pumped Rb. The NMR line can be detected at frequencies as low as 200 Hz. At fields below about 2 mT the longitudinal relaxation time saturates at about 2000 s. Two recent experiments in other laboratories have extended these pulsed NMR techniques to higher temperatures and smaller samples. In the first, images were obtained of mineral oil floating on water at room temperature. In the second, a SQUID configured as a thin film gradiometer was used to detect NMR in a 50 microm particle of 195Pt at 6 mT and 4.2 K.

Randomised controlled trial of tyrosine supplementation on neuropsychological performance in phenylketonuria.

OBJECTIVE: To test the efficacy of tyrosine supplementation, as an adjunct to dietary treatment, on neuropsychological test performance in individuals with phenylketonuria. DESIGN: A randomised controlled trial of tyrosine supplementation using a double blind crossover procedure with three four week phases. SETTING: The Hospital for Sick Children, Toronto. PARTICIPANTS: 21 individuals with phenylketonuria (ages 6 to 28 years, mean 11.3). INTERVENTION: Participants were given 100 mg/kg body weight/d of L-tyrosine or L-alanine (placebo). RESULTS: At baseline, performance on several of the neuropsychological test measures was correlated with tyrosine levels. Dietary supplements of tyrosine increased plasma tyrosine concentrations; however, no change in test performance was found across the tyrosine and placebo phases of the study. CONCLUSIONS: Tyrosine supplementation of this type does not appear to alter neuropsychological performance in individuals with phenylketonuria.

Academic validation of prior and experiential learning: evaluation of the process.

This report is a summary of an AP(E)L evaluative research project conducted at the University of Southampton School of Nursing and Midwifery. The project aimed to shed light on the perceptions of candidates and teachers in conjunction with the effectiveness of the accreditation process. Through initial semi-structured interviews with teachers (n = 6) and candidates (n = 6) offering their perceptions and experiences, an emergent questionnaire was sent to the remaining active accreditation candidates (n = 60, response n = 39) and advisers/assessors (n = 36), response n = 32). The effectiveness of candidate preparation for beginning an accreditation claim, the comprehensiveness of the types of credit available to capture learning through experience, the styles of advising and feedback from assessment are all reported on. Interestingly, the data highlight how preparing an accreditation claim can affect both adviser and candidate, in terms of being more self-critical and reflective in their areas of practice.

Effect of vitamin C supplementation on hepatic cytochrome P450 mixed-function oxidase activity in streptozotocin-diabetic rats.

The effect of vitamin C supplementation on hepatic cytochrome P450 expression was investigated in streptozotocin (STZ) diabetic male Wistar Albino rats. STZ-treated rats displayed the usual characteristics of diabetes including; hyperphagia, polydipsia, decreased body weight gain and also the increased expression and activity of hepatic CYP1A, 2B, 2E and 4A proteins. Vitamin C administration in drinking water (2% w/v) was associated with significant decreases in the levels of hyperglycaemia (P < 0.05), glycosylated haemoglobin (P < 0.05), hyperlipidaemia (P < 0.001), and hyperketonaemia (P < 0.001) associated with STZ-diabetes. Vitamin C-treatment selectively reduced the activity and expression of CYP2E proteins (P < 0.001). These effects on CYP2E expression may be mediated by the reduced levels of circulating ketone bodies, however, a direct effect on CYP2E expression in diabetes cannot be discounted.

Teaching clinical hypnosis in U.S. and Canadian dental schools.

This paper reports the results of a 1995 survey of the teaching of hypnosis in U.S. and Canadian dental schools. Responses were received from 50 schools (78%). The results are compared with prior surveys by Parrish (1973) and Simpson, Dedmon, Logan and Jakobsen (1980). The number of complete courses in hypnosis increased from 1973 to 1980 but has remained static since then. The number of other courses in which a one to two hour introduction to hypnosis is presented increased from 18% in 1980 to 30% in 1995. However, during approximately that same period (1982-1995) dentist membership in A.S.C.H. dropped from 14.9% to 4.4%. Some commentary on this phenomenon and needed future studies are offered.

Characteristics of skeletal muscle chloride channel C1C-1 and point mutant R304E expressed in Sf-9 insect cells.

Using the baculovirus system, the skeletal muscle chloride channel, CIC-1 (rat), and a point mutant replacing arginine 304 with glutamic acid were expressed at high levels in cultured Sf-9 insect cells. Whole-cell patch-clamping revealed large inwardly rectifying currents with maxima up to 15 nA inward and 2.5 nA outward. Saturation was evident at voltage steps positive to +40 mV whilst steps negative to -60 mV produced inactivating currents made up of a steady state component and two exponentially decaying components with tau 1 = 6.14+/- 0.92 ms, tau 2 = 36.5+/- 3.29 ms (S.D) n = 7 for steps to -120 mV. Currents recorded in the outside-out patch configuration were often unexpectedly large and up to 5% of whole-cell currents obtained in the same cell, suggesting an uneven channel distribution in the plasmalemma of Sf-9 cells. The pharmacology of a number of chloride channel blockers, including anthracene-9-carboxylate (A9C), niflumate, and perrhenate, was investigated and showed for the first time that perrhenate is an effective blocker of C1C-1 and that it has a complex mechanism of action. Further, the potency of A9C was found to be dependent on external chloride concentration. As in studies on muscle cells themselves, blockade was rapidly effective and easily reversible, except when applying the indanyloxyacetate derivative, IAA94/95, which took up to 10 min to act, and, consistent with an intracellular site of action, was difficult to reverse by washing. Mutation of the highly conserved arginine at position 304 to a glutamic acid did not significantly alter the behaviour of the channel.