Impact of local heating and cooling on skeletal muscle transcriptional response related to myogenesis and proteolysis.

PURPOSE: To determine the impact of local muscle heating and cooling on myogenic and proteolytic gene responses following resistance exercise. METHODS: Recreationally trained males (n = 12), age 25.3 ± 1.5, % body fat 13.6 ± 1.92, completed four sets of 8-12 repetitions of unilateral leg press and leg extension while heating one leg, and cooling the other. Muscle biopsies were taken from the vastus lateralis of each leg pre and 4 h post exercise. RESULTS: MyoD, FOXO1, and MuRF1 mRNA increased with exercise regardless of temperature (p < 0.05). Myostatin, MYF5, and atrogin-1 mRNA decreased with exercise regardless of temperature (p < 0.05). Myogenin, MRF4, and CASP3 mRNA were higher in the hot condition, compared to the cold (p < 0.05). PAX7 mRNA was lower in the hot compared to cold condition (p = 0.041). FOXO3 mRNA was higher in the cold compared to hot condition (p = 0.037). AKT1 and AKT2 were unaffected by either exercise or temperature. Femoral artery blood flow volume was higher in the hot (375.2 ± 41.2 ml min- 1), compared to the cold condition (263.5 ± 23.9 ml min- 1), p = 0.01. Tissue oxygen saturation was higher in the hot (71.7 ± 4.8%) than cold condition (55.3 ± 5.0%). CONCLUSION: These results suggest an impaired muscle growth response with local cold application compared to local heat application.

Medicines can affect thermoregulation and accentuate the risk of dehydration and heat-related illness during hot weather.

WHAT IS KNOWN AND OBJECTIVE: Hot days are increasingly common and are often associated with increased morbidity and mortality, especially in the elderly. Most heat-related illness and heat-related deaths are preventable. COMMENT: Medicines may accentuate the risk of dehydration and heat-related illness, especially in elderly people taking multiple medicines, through the following mechanisms: diuresis and electrolyte imbalance, sedation and cognitive impairment, changed thermoregulation, reduced thirst recognition, reduced sweat production, and hypotension and reduced cardiac output. WHAT IS NEW AND CONCLUSION: Commonly used medicines that may significantly increase the risk include diuretics, especially when combined with an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), anticholinergics and psychotropics. Initiation of individualized preventive measures prior to the start of the hot weather season, which includes a review of the patient and their medicines to identify thermoregulatory issues, may reduce the risk of heat-related illness or death.

Educating parents about youth suicide: knowledge, response to suicidal statements, attitudes, and intention to help.

This study evaluated the video Youth Suicide: Recognising the Signs as a parent educational medium. Before and after viewing the video, parents (N = 112) of young people answered questionnaires measuring their (1) knowledge of suicidal signs, (2) responses to a young person showing suicidal signs, (3) attitude to suicide, and (4) intentionalitv toward suicidal people. After the video, parents' knowledge of suicidal signs, responses toward a suicidal person, and intention to help improved. Their attitude was more rejecting of suicide. Knowledge and intentionality predicted response to suicidal statements, but no relationships existed between attitude and the other variables. Implications for youth suicide education programs are discussed.

Palladium-catalysed cross-coupling reactions in supercritical carbon dioxide.

Heck and Suzuki reactions proceed in good yield in supercritical carbon dioxide in the presence of palladium acetate and tri-tert-butylphosphine with both free and polymer-tethered substrates.

Use of the Mollon-Reffin minimalist color vision test with young children.

PURPOSE: We evaluated the Mollon-Reffin Minimalist (M-R M) color vision test to determine how successfully young children can perform the task and to compare success rates with the American Optical Hardy Rand Rittler (HRR) test and a preferential-looking type test based on the F2 plates (the Pease-Allen color test [PACT]). METHODS: Participants included 146 children (aged 3-10 years) and 32 older subjects (aged 11-39 years). The M-R M test uses 3 series of colored caps coinciding with protan, deutan, and tritan confusion axes, with 6 saturations along each axis. The observer must identify a single colored cap from gray caps of varying lightness. The PACT test consists of 2 cards with targets for detecting red-green and blue-yellow color deficiencies. The tester judges the location of the target on the basis of the child's looking and/or pointing responses. The HRR was performed according to standard instructions, although a more flexible scoring protocol was also used. RESULTS: A significant difference in the children's performance between the "test" item of the 3 tasks emerged (Cochran Q test, P<.001): all children successfully completed the M-R M, 90% successfully completed the PACT, and 88% successfully completed the HRR. Few errors were made on the M-R M red-green series, even among children aged 3 to 4 years, although errors were made with the least saturated blue-yellow cap at all ages. Recommendations are made for the use of the M-R M with children. CONCLUSIONS: The M-R M test can be performed by young children and may prove to be especially useful for detecting and monitoring acquired color vision defects.

An Australian study of adolescents with cystic fibrosis: perceived supportive and nonsupportive behaviors from families and friends and psychological adjustment.

PURPOSE: To identify and compare perceived supportive and nonsupportive behaviors exhibited by family members and friends toward adolescents with cystic fibrosis (CF), and to examine the relationships between supportive and nonsupportive behaviors and adolescents' psychological adjustment. METHOD: Participants were 35 adolescents with CF attending the Women's and Children's Hospital in South Australia. Perceived supportive and nonsupportive behaviors were assessed using an adapted version of the Chronic Disease Support Interview. The psychological adjustment of the adolescents was assessed using the Youth Self Report Form. Repeated-measures analyses of variance were performed to compare the support provided by family members and friends. Multiple regression analyses assessed the contribution of supportive and nonsupportive behaviors for the prediction of psychological adjustment. RESULTS: Family members provided more tangible support than friends who, conversely, provided more companionship support. Overall, family members scored higher than friends on ratings for supportive behaviors. No differences were observed between family members and friends on ratings for nonsupportive behaviors. Rating of nonsupportive behaviors for family members was found to be the strongest predictor of psychological adjustment. CONCLUSIONS: Family members and friends provide different types of support. Family members provide more tangible help with treatment tasks and adolescents provide more companionship. Overall, this study demonstrated the importance of addressing nonsupportive as well as supportive behaviors when investigating the impact of support on the psychological adjustment of adolescents with a chronic illness.

Children's eyewitness memory for a repeated event.

OBJECTIVE: This study examined a significant issue for chronic sexual abuse investigations: Children's eyewitness testimony about repeated events. The few previous studies focused on preschoolers and none used the present methodology of presenting repeated events differing slightly in their details, as would happen in chronic abuse. METHOD: One group of 6- to 7-year-olds played individually with an experimenter on one occasion; the other group experienced three such events, with some details remaining the same and others changing. In a phased interview, children were questioned about the initial event. RESULTS: For details which stayed the same, the children who experienced three events had more accurate memories. They had poorer memories than the single-event group for details which were changed in the later events; however, this was due to interference errors, with errors of omission and commission being lower than in the single-event group. Children conveyed clearly that inappropriate touching did not occur. CONCLUSIONS: Children who experience repeated events have increased recall for repeated details but confuse the timing of details which change across events. The findings support previous suggestions that (a) it is unrealistic to expect children to be able to report repeated events without some confusion about timing of details and (b) children are resistant to misleading questions about abuse.

Youth suicide: the knowledge and attitudes of Australian teachers and clergy.

This is the first study of the suicide-related knowledge and attitudes of teachers and clergy in Australia. These professional groups have been identified as "gatekeepers" who might serve as a first line of assistance for distressed young people. Such gatekeepers, along with medical and mental health professionals, have a vital role to play in the prevention of youth suicide, of which Australia has the highest rates in the world. This research confirmed that high numbers of teachers and clergy have been approached by suicidal young persons. However, their gatekeeping role may be compromised by a low level of knowledge about signs of suicide risk, which was found even among those who had taken courses in suicide or death and dying or who had personally known someone who suicided. Suicidal behavior was found to be generally regarded as unacceptable, especially by those with a high religious commitment. Further educational efforts about suicide risk identification and prevention seem to be needed for both teachers and clergy; it will be important for such education to take into account attitudinal issues and how these might affect communication with young suicidal people.

The development of the Louis MACRO (Mother and Child Risk Observation) forms: assessing parent-infant-child risk in the presence of maternal mental illness.

OBJECTIVE: The theoretical framework and psychometric properties of the MACRO (Mother and Child Risk Observation) 1 and 2 forms (age 0 to 4 year) are presented. The MACRO forms provide ratings on five domains--three related to parenting, two on infant (or child) characteristics and maternal mental state. Case vignettes illustrate their clinical utility. METHOD: Ratings on the MACRO of 110 mother-infant and 85 mother-toddler consecutive admissions to a South Australian psychiatric in-patient mother-infant unit provided data on internal consistency, interrater, and test-retest reliability. RESULTS: Internal consistency was between .79 and .95 for all MACRO domains. Item-total correlations were between .39 and .90 with the exception of one item. Social Support. Distributions of item scores indicated acceptable discrimination. Interrater reliability was .79 or above for all domains. Test-retest reliability after 7 days was .71 or above. CONCLUSIONS: Preliminary psychometric investigations of the MACRO was favorable. Should further validity investigations prove satisfactory, the MACRO will provide a valuable clinical and research tool. The MACRO offers a convenient framework for assessing risk and interpreting the impact of maternal mental illness upon children within a context that permits consideration of factors such as illness severity, parenting practices, and child contribution to outcome.

The effect of nursing education and experience on attitudes to diabetes.

The diabetes-related attitudes of 629 nurses working in South Australian hospitals were identified in a study using a questionnaire that included the revised Diabetes Attitudes Scale. Overall, the nurses' attitudes were appropriate; some were found to be related to levels of nursing education and others to nursing experience. There were significant differences between some attitudes held by nurses and previously reported attitudes of pre-registration nursing students. This study indicates that formal nursing education affects nurses' attitudes to diabetes and implications of the findings for inservice diabetes programs are discussed.

Changing students' attitudes to diabetes.

In a cross-sectional study, the appropriateness of attitudes of first, second and third year undergraduate nursing students to seven aspects of diabetes care were measured using the revised Diabetes Attitude Scale. The aim of the research was to identify changes in the students' attitudes and to examine the relationship between attitudinal changes and the exposure of students to diabetes-related education. The study found that attitudes of graduating students to five aspects of the care of people with diabetes were significantly more appropriate than those of beginning students. It was concluded that exposure to diabetes education had been the major factor in engendering attitudes that underlie positive nursing approaches to the health care of people with diabetes.

Measuring diabetes-related attitudes: the use of a USA-developed instrument with Australian nurses.

The revised Diabetes Attitudes Scale (DAS) was completed by nearly 1000 nurses and nursing students in South Australia. Confirmatory factor analysis was used to compare the factor structure with that previously obtained in the USA with patients with diabetes. The instrument was found to be robust. It was concluded that only one item of the 50-item scale is unsuitable for inclusion in studies which aim to compare patient and health professional attitudes.

Assessment of peer relationships in children with asthma.

Identified peer relationships in children with chronic illnesses as an important but neglected, research area. This study compared 21 children with asthma, ages 8-13, with 21 matched classroom controls on a number of measures of peer relationship adjustment, including both self-report and peer-report items. Overall, the children with asthma had peer relationships that were equivalent to those of their classmates, although they were seen as being sicker and missing more school. However, those children who experienced more hospitalizations were less preferred as playmates, perceived as more sensitive-isolated, and felt more lonely. Implications for intervention are considered, and the notion of asthma severity and its measurement is also discussed.

OKN asymmetries in orthoptic patients: contributing factors and effect of treatment.

Monocular optokinetic nystagmus (MOKN) was measured (EOG) in response to horizontally moving square wave gratings (0.2 c/deg, 27 and 35 deg/s) in 58 children with amblyopia and/or strabismus (experimental group); the data were compared with that collected from 24 children (aged 3-8 years) with no visual problems (control group). We found OKN asymmetries most often associated with strabismus of early age of onset (less than 2 years). In these children the MOKN asymmetry often occurred in both eyes. In children with later onset strabismus the asymmetry was often confined to the amblyopic eyes. We repeated the measurements on 18 experimental children after 1-3 years of treatment (patching the dominant eye) and compared the results with those recorded in 12 fully binocular control children retested after 1-2 years. Large OKN asymmetries before treatment were still present after the patching treatment. However there was a small, but significant (P = 0.05, t-test), improvement in the nasal-temporal (N-T) slow-phase velocity in the affected eyes of the experimental group, which was not correlated with improvements in visual acuity or linked to the presence of strabismus and/or amblyopia. The main contributing factors to asymmetric OKN affecting both eyes of early onset strabismus seem to be to poor binocularity which would not improve during patching treatment. OKN asymmetries in amblyopic eyes may also result from reduced cortical sensitivity from that eye, which may be minimally improved by patching treatment. Our results suggest a shorter sensitive period of development for OKN pathways than for the development of cortical visual pathways.

Visual fitness to drive after stroke or head injury.

The visual requirements for driving in Britain are outlined and how they might be compromised following stroke or head injury examined. The role of the optometrist in assessing such patients who wish to resume driving is discussed. Topics discussed include legal considerations, the relationship between visual problems and driving ability and the vision-testing techniques that are most appropriate for use with the brain injured. An illustrative case history is presented.

Success rates in testing monocular acuity and stereopsis in infants and young children.

This study demonstrated how success in stereopsis and monocular acuity testing in the under-fives changes with age. Monocular testing was least successful with 1-2-year olds, while success with stereopsis testing increased linearly to 100% by 3 years. The differing patterns mean that a reasonable degree of success with one test or the other is likely whatever a child's age. Since the demonstration of either stereopsis or normal monocular acuities rules out the presence of any gross visual anomaly, the age-appropriate use of the two types of testing will facilitate the early detection of any abnormality.

Affinity purification of the novel cysteine proteinase papaya proteinase IV, and papain from papaya latex.

A procedure is described for the purification of a previously undetected cysteine proteinase, which we have called papaya proteinase IV, from spray-dried latex of the papaya (Carica papaya) plant. The purification involves affinity chromatography on Gly-Phe-aminoacetonitrile linked to CH-Sepharose 4B, with elution by 2-hydroxyethyl disulphide at pH 4.5. The product thus obtained is a mixture of almost fully active papain and papay proteinase IV, which are then separated by cation-exchange chromatography. A preliminary characterization of papaya proteinase IV showed it to be very similar to chymopapain in both molecular size and charge. However, the new enzyme is immunologically distinct from the previously characterized cysteine proteinases of papaya latex. It also differs in its lack of activity against the synthetic substrates of the other papaya proteinases, in its narrow specificity against protein substrates and its lack of inhibition by chicken cystatin. Papaya proteinase IV is abundant, contributing almost 30% of the protein in spray-dried papaya latex, and contamination of chymopapain preparations with this enzyme may account for some of the previously reported heterogeneity of chymopapain.

Highly conformationally constrained halogenated 6-spiroepoxypenicillins as probes for the bioactive side-chain conformation of benzylpenicillin.

The halogenated 6-spiroepoxypenicillins are a series of novel semisynthetic beta-lactam compounds with highly conformationally restricted side chains incorporating an epoxide. Their biological activity profiles depend crucially on the configuration at position C-3 of that epoxide. In derivatives with aromatic-containing side chains, e.g., anilide, the 3R-compounds possess notable Gram-positive antibacterial activity and potent beta-lactamase inhibitory properties. The comparable 3S-compounds are antibacterially inactive, but retain beta-lactamase inhibitory activity. Using the molecular simulation programs COSMIC and ASTRAL, we attempted to map a putative, lipophilic accessory binding site on the PBPs that must interact with the side-chain aromatic residue. Comparative computer-assisted modelling of the 3R-, and 3S-anilides, along with benzylpenicillin, indicated that the available conformational space at room temperature for the side chains of the 3R- and the 3S-anilides was mutually exclusive. The conformational space for the more flexible benzylpenicillin could accommodate the side chains of both the constrained penicillin derivatives. By a combination of van der Waals surface calculations and a pharmacophoric distance approach, closely coincident conformers of the 3R-anilide and benzylpenicillin were identified. These conformers must be related to the antibacterial, 'bioactive' conformer for the classical beta-lactam antibiotics. From these proposed bioactive conformations, a model for the binding of benzylpenicillin to the PBPs relating the three-dimensional arrangement of a putative lipophilic S2-subsite, specific for the side-chain aromatic moiety, and the 3 alpha-carboxylate functionality is presented.

Analogues of the cytostatic and antimitogenic agents chlamydocin and HC-toxin: synthesis and biological activity of chloromethyl ketone and diazomethyl ketone functionalized cyclic tetrapeptides.

The synthesis and biological activity of four novel analogues of the cytostatic and antimitogenic agents chlamydocin and HC-toxin are reported in which the natural products' reactive epoxy ketone side-chain moiety is replaced by a chloromethyl or a diazomethyl ketone functionality, but the respective 12-membered cyclic tetrapeptide ring systems are retained. Syntheses of the linear tetrapeptide sequences were, in each case, achieved by conventional methodology and designed such that cyclization would be onto proline. The use of suitably protected L-2-aminosuberic acid (Asu) enabled the ready assimilation of the desired chloromethyl and diazomethyl ketone functionalities after cyclization. Cyclization was accomplished by using bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl). Yields of cyclic product were comparable to or, in the case of the HC-toxin ring system, better than those previously reported. Liberation of the Asu-side-chain acid and manipulation to the required functionalities via mixed anhydride to the diazomethyl ketone and quenching with HCl to yield the chloromethyl ketone was achieved in excellent yield for the HC-toxin analogues but in only moderate yield for the chlamydocin analogue. The antimitogenic activities of HC-toxin chloromethyl ketone (IC50 = 30-40 ng/mL) and chlamydocin chloromethyl ketone (IC50 = 3-10 ng/mL) were found to be 3-4-fold lower than those of the natural products themselves. The diazomethyl ketone analogue of HC-toxin was found to be inactive (IC50 greater than 2000 ng/mL). A modification of the HC-toxin peptide ring system, [L-Phe]3-HC-toxin chloromethyl ketone was found not to be a more active analogue (IC50 = 40-100 ng/mL). The nature of the putative target molecule, the binding interactions of the various analogues and the contribution of rate of inhibition toward activity are briefly discussed. The chloromethyl ketones herein reported constitute the most potent synthetic antimitogenic cyclic tetrapeptide analogues yet designed.