Carers' perspectives of a weight loss intervention for adults with intellectual disabilities and obesity: a qualitative study.

BACKGROUND: To date, no studies have explored the role of carers in supporting adults with intellectual disabilities (ID) and obesity during a weight loss intervention. The present study explored perceptions of carers supporting adults with ID, as they participated in a 6-month multi-component weight loss intervention (TAKE 5). METHODS: Semi-structured interviews were used to explore the experiences of 24 carers. The transcripts were analysed qualitatively using thematic analysis. RESULTS: Three themes emerged from the analysis: carers' perceptions of participants' health; barriers and facilitators to weight loss; and carers' perceptions of the weight loss intervention. Data analysis showed similarities between the experiences reported by the carers who supported participants who lost weight and participants who did not. Lack of sufficient support from people from the internal and external environment of individuals with ID and poor communication among carers, were identified as being barriers to change. The need for accessible resources tailored to aid weight loss among adults with ID was also highlighted. CONCLUSION: This study identified specific facilitators and barriers experienced by carers during the process of supporting obese adults with ID to lose weight. Future research could utilise these findings to inform appropriate and effective weight management interventions for individuals with ID.

The 39-kilodalton subunit of eukaryotic translation initiation factor 3 is essential for the complex's integrity and for cell viability in Saccharomyces cerevisiae.

Eukaryotic translation initiation factor 3 (eIF3) in the yeast Saccharomyces cerevisiae comprises about eight polypeptides and plays a central role in the binding of methionyl-tRNAi and mRNA to the 40S ribosomal subunit. The fourth largest subunit, eIF3-p39, was gel purified, and a 12-amino-acid tryptic peptide was sequenced, enabling the cloning of the TIF34 gene. TIF34 encodes a 38,753-Da protein that corresponds to eIF3-p39 in size and antigenicity. Disruption of TIF34 is lethal, and depletion of eIF3-p39 by glucose repression of TIF34 expressed from a GAL promoter results in cessation of cell growth. As eIF3-p39 levels fall, polysomes become smaller, indicating a role for eIF3-p39 in the initiation phase of protein synthesis. Unexpectedly, depletion results in degradation of all of the subunit proteins of eIF3 at a rate much faster than the normal turnover rates of these proteins. eIF3-p39 has 46% sequence identity with the p36 subunit of human eIF3. Both proteins are members of the WD-repeat family of proteins, possessing five to seven repeat elements. Taken together, the results indicate that eIF3-p39 plays an important, although not necessarily direct, role in the initiation phase of protein synthesis and suggest that it may be required for the assembly and maintenance of the eIF3 complex in eukaryotic cells.

SUI1/p16 is required for the activity of eukaryotic translation initiation factor 3 in Saccharomyces cerevisiae.

A genetic reversion analysis at the HIS4 locus in Saccharomyces cerevisiae has identified SUI1 as a component of the translation initiation complex which plays an important role in ribosomal recognition of the initiator codon. SUI1 is an essential protein of 12.3 kDa that is required in vivo for the initiation of protein synthesis. Here we present evidence that SUI1 is identical to the smallest subunit, p16, of eukaryotic translation initiation factor 3 (eIF-3) in S. cerevisiae. SUI1 and eIF3-p16 comigrate upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis and cross-react with anti-SUI1 and anti-eIF3 antisera. Anti-SUI1 antisera immunoprecipitate all of the subunits of eIF3, whereas antisera against the eIF3 complex and the individual PRT1 and GCD10 subunits of eIF3 immunoprecipitate SUI1. Finally, the N-terminal amino acid sequence of a truncated form of eIF3-p16 matches the sequence of SUI1. eIF3 isolated from a sui1(ts) strain at 37 degrees C lacks SUI1 and fails to exhibit eIF3 activity in the in vitro assay for methionyl-puromycin synthesis. A free form of SUI1 separate from the eIF3 complex is found in S. cerevisiae but lacks activity in the in vitro assay. The results, together with prior genetic experiments, indicate that SUI1 is essential for eIF3 activity and functions as part of eIF3 and in concert with eIF2 to promote eIF2-GTP-Met-tRNAi ternary complex recognition of the initiator codon.

Mn2+-uncoupling of the catecholamine-sensitive adenylate cyclase system of rat reticulocytes. Parallel effects on cholera toxin-catalyzed ADP-ribosylation of the system.

High concentrations of Mn2+ interfere with functional interactions between the GTP-binding regulatory protein (G) and the catalytic moiety (C) of adenylate cyclase without perturbing interactions between receptor (R) and component G in rat reticulocyte membranes. The ability of cholera toxin to ADP-ribosylate component G and to enhance GTP-stimulated adenylate cyclase activity also appears to be correlated with the efficacy of the communication of component G with the adenylate cyclase system. Thus, increasing the concentration of Mn2+ in rat reticulocyte membrane during in vitro incubations causes a parallel loss of Gpp(NH)p-stimulated adenylate cyclase activity, cholera toxin-catalyzed [32P]ADP-ribosylation of the 42 000 Mr subunit of component G and cholera toxin-catalyzed enhancement of GTP-sensitive adenylate cyclase activity. Removal of Mn2+ by washing the membranes completely restores the sensitivity of adenylate cyclase activity. Removal of Mn2+ by washing the membranes completely restores the sensitivity of adenylate cyclase to all effectors, including cholera toxin. The data suggest that exposure of membranes to Mn2+ provides a useful tool for reversibly uncoupling catecholamine-sensitive adenylate cyclase systems. The data also suggest that the extent of cholera toxin-catalyzed ADP.-ribosylation of membrane substrates, i.e., the G component may rely on functional communication among the various components of the adenylate cyclase system. A corollary of the latter is that the amount of [32P]ADP-ribose-product detected in a membrane may reflect both the quantity and coupling efficiency of component G.

The ion coupling and organic substrate specificities of osmoregulatory transporter ProP in Escherichia coli.

Transporter ProP of Escherichia coli, a member of the major facilitator superfamily, mediates osmoprotective proline or glycine betaine accumulation by bacteria exposed to high osmolality environments. Morpholinopropane sulfonic acid, a common constituent of microbiological media, accumulates in osmoadapting E. coli cells but it is not osmoprotective and it did not influence proP transcription or ProP activity. The apparent K(m) for proline uptake via ProP increased with decreasing pH in the range 7.5-4. ProP-dependent proline uptake by de-energized bacteria was associated with alkalinization of the external medium. Thus ProP mediates cotransport of H(+) and zwitterionic proline and a transporter functional group with a pK(a) of 5-6 is implicated in catalysis. Exogenous proline or glycine betaine elicits K(+) release from osmoadapting E. coli cells and ProP activity is stimulated by exogenous K(+). However, uptake of proline or glycine betaine stimulated K(+) efflux from K(+)-loaded bacteria which expressed either ProP or alternative, osmoregulatory transporter ProU. This indicated that ProP was unlikely to mediate K(+) efflux. Zwitterions ectoine, pipecolate, proline betaine, N,N-dimethylglycine, carnitine and 1-carboxymethylpyridinium were identified as alternative ProP substrates. Choline, a cation and a structural analogue of glycine betaine, was a low affinity inhibitor but not a substrate of ProP.

YAC/STS map of 15Mb of Xp21.3-p11.3, at 100kb resolution, with refined comparisons of genetic distances and DMD structure.

The 15Mb region between DXS997 and DXS8054 in Xp21.3-p11.3 has been mapped at seven-fold average coverage in yeast artificial chromosomes (YACs) and 100 kb inter-sequence tagged site (STS) distance. YACs from six different collections show self-consistent maps. The STSs include 18 (CA) repeat and one tetranucleotide repeat marker that detect polymorphism, as well as eight well-studied genes, a second site for MXS1 sequences, and three expressed sequence tags (ESTs). One of the ESTs maps to intron 7 of Duchenne muscular dystrophy, and seems to be a processed intronic sequence with a poly(A) tail.

Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex.

The initiation of translation on eukaryotic mRNA is governed by the concerted action of polypeptides of the eIF-4F complex. One of these polypeptides, eIF-4G, is proteolytically inactivated upon infection with several members of the Picornaviridae family. This cleavage occurs by the action of virus-encoded proteinases: 2Apro (entero- and rhinovirus) or Lpro (aphthovirus). An indirect mode of eIF-4G cleavage through the activation of a second cellular proteinase has been proposed in the case of poliovirus. Although cleavage of eIF4G by rhino- and coxsackievirus 2Apro has been achieved directly in vitro, a similar activity has not been documented to date for poliovirus 2Apro. We report here that a recombinant form of poliovirus 2Apro fused to maltose binding protein (MBP) directly cleaves human eIF-4G from a highly purified eIF-4F complex. Efficient cleavage of eIF-4G requires magnesium ions. The presence of other initiation factors such as eIF-3, eIF-4A or eIF-4B mimics in part the stimulatory effect of magnesium ions and probably stabilizes the cleavage products of eIF-4G generated by 2Apro. These results suggest that efficient cleavage of eIF4G by MBP-2Apro requires a proper conformation of this factor. Finally, MBP-2Apro protein cleaves an eIF-4G-derived synthetic peptide at the same site as rhino- and coxsackievirus 2Apro (R485-G486).

Afferent volley patterns and the spinal release of immunoreactive substance P in the dorsal horn of the anaesthetized spinal cat.

Microprobes bearing immobilized antibodies to the C-terminus of substance P were used to measure release of this neuropeptide in the spinal cord of the anaesthetized spinal cat in response to peripheral nerve stimulation. Release of substance P was just detectable in laminae I, II with 150 stimuli (0.5 Hz, 5 min) and was near maximal with 300 stimuli. Using two periods of stimulation of 10 min separated by 15 min, greater levels of substance P were detected during the second period. Fifteen to 25 min after two periods of peripheral nerve stimulation levels of substance P detected by microprobes were still elevated above those present prior to stimulation. Stimulation with bursts of three impulses when delivering a fixed number of stimuli resulted in detection of increased levels of substance P at sites adjacent to the areas of maximal release. The results suggest that maximal release of substance P from the central terminals of primary afferent fibres occurs with relatively few impulses and at low frequencies in agreement with what is known of release from the peripheral terminals of these fibres.

A comparison of the effects of SCA40, NS 004 and NS 1619 on large conductance Ca(2+)-activated K+ channels in bovine tracheal smooth muscle cells in culture.

1. The effects of imidazopyrazine derivative, SCA40, on the activity of single large conductance, Ca(2+)-activated K+ (BKCa) channels in inside-out and outside-out patches from bovine tracheal smooth muscle (BTSM) cells in culture have been compared with those of two established BKCa channel openers, NS 004 and NS 1619. 2. The presence of BKCa channels on inside-out patches of BTSM membranes was confirmed by the single channel conductance (240 pS), selectivity for K+, dependence of channel activity on [Ca2+]i, and sensitivity to the selective BKCa channel blocker, iberiotoxin. 3. NS 004 and ND 1619 (3-30 microM) induced concentration-related increases in open state probability of BKCa channels when applied to either inside-out or outside-out BTSM patches, thus confirming that these compounds are activators of the BKCa channel in this preparation. 4. SCA40 (0.1-10 microM) had no effect on the activity of BKCa channels when applied to either inside-out or outside-out patches which subsequently responded to the application of NS 004 (10-20 microM). 5. It is concluded that SCA40 does not have a direct effect on BKCa channel activity in BTSM patches and that the previously reported relaxant action of SCA40 on tracheal smooth muscle is unlikely to be mediated by this mechanism.

Effects of the kappa-opioid agonist U50,488 on parturition in rats.

1. The effects of the kappa-opioid agonist U50,488 on parturition were studied in the rat. 2. Given directly after the birth of the second pup U50,488 (5 mg or 10 mg kg-1, i.p.) delayed the birth of the subsequent 4 pups by ca. 100 min, acting like morphine (10 mg kg-1, i.p.). In controls given the vehicle i.p., the birth of the 4 pups after treatment took 45.4 +/- 4.6 min. The effects of U50,488 could be prevented by simultaneous naloxone injection (10 mg kg-1). Injection of either U50,488 or morphine at 1 mg kg-1, i.v. also significantly delayed parturition. The effects of U50,488 but not of morphine were fully prevented by preinjection with nor-binaltorphimine (0.5 mg kg-1, i.v.) showing selective kappa-opioid receptor-mediated inhibition by U50,488 of established parturition. 3. In rats with an indwelling jugular venous cannula, i.v. injection of U50,488 (5 mg kg-1) after the birth of the second pup slowed parturition in a similar way to i.p. injection and significantly reduced blood plasma oxytocin concentration measured by radioimmunoassay compared with vehicle-injected controls. 4. Bolus i.v. injections of oxytocin (4 mu once per 5 min) significantly reduced the delay in parturition caused by i.v. U50,488, but continuous i.v. infusion of oxytocin (4 mu 5 min-1) was less effective. 5. Since i.v. oxytocin did not immediately reverse the effects of U50,488 on parturition, direct effects of U50,488 on isometric uterine contractions in vitro were sought. U50,488 inhibited spontaneous or oxytocin-stimulated contractions of uteri from rats within 24 h after parturition in a dose-related manner; the inhibitory effect was not naloxone-reversible.6. Thus U50,488 inhibited established parturition in the rat in a Kappa-opioid selective manner by reducing oxytocin secretion. The inhibitory effect may well have been potentiated by a direct non-opioid depressant action on contractile activity of the uterus.

Early feeding and the incidence of gastrointestinal symptoms after major gynecologic surgery.

OBJECTIVE: To compare early feeding with traditional postoperative dietary management for development of postoperative gastrointestinal symptoms, including ileus after major gynecologic surgery for benign conditions. METHODS: Women who had major gynecologic surgery for benign conditions were randomly allocated to early feeding of low residue diets 6 hours postoperatively or traditional dietary management of clear liquids with normal bowel sounds, and regular diet with passage of flatus. Demographic and perioperative data were collected, and patients answered questionnaires on their perception of bowel function and pain using the McGill Pain Scale. Power analysis found that 130 women were needed to find a twofold greater incidence of ileus in the early feeding group with 80% power and alpha =.05. RESULTS: Complete data were available for 139 women, 67 allocated to the early feeding group and 72 to the late feeding group. The incidence of postoperative ileus for the study population was 4.4% and did not differ between groups (early 3% versus late 5. 8%, P =.68). There were no differences in patient demographics, surgical procedures, anesthesia used, and intraoperative complications between groups. With the exception of more complaints of nausea in the late feeding group (23% versus 13%, P =.04), there were no differences in other postoperative variables, including other perioperative complications, pain medicine requirements, fluid and caloric intake, median pain scores, and gastrointestinal function. The low incidence of perioperative complications made the power to detect differences between groups low. CONCLUSION: Low residue diet 6 hours after major gynecologic surgery for benign indications was not associated with increased postoperative gastrointestinal complaints, including ileus.

Case study: caudate glutamatergic changes with paroxetine persist after medication discontinuation in pediatric OCD.

Proton magnetic resonance spectroscopy (1H-MRS) was used to examine glutamatergic (Glx) abnormalities in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD), associated with severity of illness and response to acute (12 weeks) treatment with paroxetine. In this report, OCD symptoms improved markedly in an 8-year-old girl treated for 14 months with the selective serotonin reuptake inhibitor paroxetine (titrated from 10 to 40 mg/day). Paroxetine dose was then decreased in 10-mg decrements and discontinued without symptom recurrence. Serial 1H-MRS examinations were acquired before and after 12 weeks of paroxetine treatment (40 mg/day) and 3 months after medication discontinuation. A striking decrease in caudate Glx was observed after 12 weeks of treatment which persisted after medication discontinuation. These data provide further support for a reversible glutamatergically mediated dysfunction of the caudate nucleus in OCD that may serve as a pathophysiological and treatment response marker.

The release of beta-endorphin and the neuropeptide-receptor mismatch in the brain.

Microprobes bearing immobilized antibodies to the carboxy-terminus of beta-endorphin were used to study the release of beta-endorphin in the urethane anaesthetized rat following electrical stimulation of the ipsilateral arcuate nucleus. The microprobes were inserted through the cerebral hemisphere, the superior colliculus and the midbrain periaqueductal grey. Since such microprobes detect extracellular molecules along their entire length they give information on the persistence and spread of compounds following release. Little immunoreactive-beta-endorphin was detected in the areas of brain sampled during electrical stimulation of arcuate nucleus but a remarkable spread throughout the midbrain and cerebral cortex occurred within 30 min of the cessation of stimulation. The results suggest that although beta-endorphin-containing fibres are absent in many parts of the brain, this neuropeptide can access receptors in these sites and it is not necessary for release to be directly adjacent to opiate receptors. As such it is important evidence supporting the hypothesis of volume transmission as a means of neuronal communication. The results also suggest that an important mechanism of the transport of beta-endorphin is the cerebrospinal fluid.

The release of immunoreactive neuropeptide Y in the spinal cord of the anaesthetized rat and cat.

The release of immunoreactive (ir-) neuropeptide Y (NYP) was studied in the anaesthetized rat and cat by means of microprobes bearing immobilized antibodies to the C terminus of NPY. An extensive basal release of ir-NYP was detected throughout the dorsal and upper ventral horn of the rat. This spontaneous release was not significantly altered by sectioning the spinal cord at the thoraco-lumbar junction nor by electrical stimulation of peripheral nerves. Since NPY is virtually absent in primary afferents it is probable that spontaneous release within the spinal cord comes from active NPY-containing intrinsic spinal neurones. In the spinal cat spontaneous release of ir-NPY was detected in the mid-dorsal horn and this was unaltered by peripheral noxious thermal or noxious mechanical stimuli. As in the rat, release from intrinsic spinal neurones is most probable. The extensive spontaneous release of ir-NPY in both species suggests a widespread role in spinal cord function.

Opioid peptides have differential actions on sub-populations of arcuate neurones.

Extracellular recordings were made from spontaneously active arcuate neurones in hypothalamic slices in vitro. The majority of these neurones (82%) were inhibited in a dose-related manner by opioid peptides added to the perfusion medium at concentrations of 0.1-100 microM. The inhibitory responses were reversed by equimolar concentrations of naloxone. In terms of their latency to 50% inhibition and duration of action the order of potency of the opioid peptides on a molar basis was beta-Endorphin greater than DAGO greater than DADLE greater than Dynorphin. Several sub-populations of arcuate neurones can be identified on the basis of their neuronal activity. Opioid peptides selectively abolished the bursts in those neurones (putative peptidergic neurones) which discharged with a combination of bursts and single irregular action potentials suggesting a selective membrane action rather than an overall hyperpolarizing influence. A population of neurones which displayed episodic or regular activity, and which had action potentials characteristic of dopamine neurones, were profoundly inhibited by the opioid peptides; the activity of a second population of regularly firing neurones with conventional action potential profiles was totally unaffected. These electrophysiological studies thus provide evidence that the arcuate nucleus is one possible site of action at which endogenous opioid peptides could exert their modulatory role on neuroendocrine function; and the predominate influence is likely to be mediated through mu receptors.

Increased medial thalamic choline in pediatric obsessive-compulsive disorder as detected by quantitative in vivo spectroscopic imaging.

The thalamus has been implicated in the pathophysiology of obsessive-compulsive disorder. Using a multislice spectroscopic imaging sequence, we reported reductions in right and left medial thalamic N-acetylaspartate/cytosolic choline + creatine/phosphocreatine and N-acetylaspartate/cytosolic choline levels in 11 pediatric patients with obsessive-compulsive disorder, 8 to 15 years, versus 11 case-matched healthy controls. These changes may reflect a change in N-acetylaspartate, cytosolic choline, or creatine concentrations. Therefore, using a validated phantom replacement methodology, we obtained absolute measures (mmol/L) of N-acetylaspartate, a putative marker of neuronal viability, cytosolic choline, and creatine in these subjects. A significant increase in cytosolic choline was observed in right and left medial but not lateral thalami in patients with obsessive-compulsive disorder versus controls. N-acetylaspartate and creatine did not differ significantly between case-control pairs in the medial or lateral thalamus. These findings provide new evidence of cytosolic choline abnormalities in the thalamus in pediatric obsessive-compulsive disorder.

Factors associated with shear bond strength of composite resin to human enamel.

The preparation of enamel surfaces before etching by removing 0.5 mm of surface tooth structure is common-place in modern restorative dentistry. This study was designed to measure and compare the shear bond strength of composite resin bonded to prepared and unprepared enamel using various proprietary bonding systems. The analysed results failed to show significant differences between the shear bond strengths of the prepared and unprepared enamel specimens. Conditioning enamel surfaces for 60 seconds using 2.5% nitric acid where the solution was allowed to desiccate, resulted in significantly lower bond strengths compared to the other regimes. A correlation of the etchant pH with the mean shear bond strength of the adhesive systems to enamel was observed. The surface topography of the etched enamel surfaces correlated moderately well with the bond strengths obtained.

Smart investments in sustainable food production: revisiting mixed crop-livestock systems.

Farmers in mixed crop-livestock systems produce about half of the world's food. In small holdings around the world, livestock are reared mostly on grass, browse, and nonfood biomass from maize, millet, rice, and sorghum crops and in their turn supply manure and traction for future crops. Animals act as insurance against hard times and supply farmers with a source of regular income from sales of milk, eggs, and other products. Thus, faced with population growth and climate change, small-holder farmers should be the first target for policies to intensify production by carefully managed inputs of fertilizer, water, and feed to minimize waste and environmental impact, supported by improved access to markets, new varieties, and technologies.