Squaric esters as peptide stapling reagents.

We report that squaric esters can serve as bifunctional reagents for selective peptide stapling reactions. Formation of the squaric amide staple occurs under mild conditions with amine-containing side chains. We show that short resin-bound peptides are readily stapled on solid phase and that stapling can occur at various relative positions along the peptide and with various amine tether lengths (e.g. Lysine, ornithine, etc). The squaric amide staples are stable to strong acid conditions used to cleave the stapled peptide from the resin and the stapled peptides show an increase in helicity as analyzed through circular dichroism.

The meaning of play for children and young people with physical disabilities: A systematic thematic synthesis.

BACKGROUND: Children and young people with physical disabilities are often reported to play less than their typically developing peers. Few studies explore the meaning of play from the child's perspective; this study carried out a thematic synthesis of the findings of qualitative studies about the meaning of play following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: A search of CINAHL, AHMED, PsycINFO, MEDLINE, EMBASE, and ERIC was undertaken between September 2015 and March 2016. Qualitative studies exploring the meaning of play from the perspective of 0- to 18-year-olds with physical disabilities impacting function were included. Quality appraisal and thematic synthesis were undertaken in order to develop analytical themes. RESULTS: Thirteen studies met the inclusion criteria in part addressing the meaning of play for children and young people with physical disabilities. Synthesis of the findings identified 5 analytical themes: Play can feel both positive and negative; play can draw attention towards or away from my disability; play is a social interaction; I participate differently to my peers, and needing help feels normal. CONCLUSIONS: The themes highlight the potential for play experiences of individuals with physical disabilities being overlooked by parents and professionals; further research is needed to explore play experience from these individual's perspective.

Erratum: One welfare: Linking poverty, equid ownership and equid welfare in the brick kilns of India - ERRATUM.

[This corrects the article DOI: 10.1017/S0962728600032504.].

In vitro correlates of transformation in C3H/10T1/2 clone 8 mouse cells.

Various potential in vitro correlates of malignancy were studied in four chemically transformed C3H/10T1/2 Clone 8 mouse cell lines and were compared with controls cells. The degree of tumorigenicity was best predicted by the relative plating efficiencies of the morphologically transformed cells in soft agar. All transformed cells also showed an increase in extracellular fibrinolytic activity which may be an additional marker for transformation. Intracellular fibrinolytic activity and loss of 125I-labeled cell surface protein (M.W. 250,000) were not correlated with morphological transformation or tumorigenicity in these cells.

Combined vitamin B6-magnesium treatment in autism spectrum disorder.

BACKGROUND: The use of mega-vitamin intervention began in the 1950s with the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used with children diagnosed with "autism syndrome" when speech and language improvement was observed in some children as a result of large doses of B6. A number of studies attempted to assess the effects of vitamin B6-Magnesium (Mg) was found to reduce undesirable side effects from B6) on characteristics such as verbal communication, non-verbal communication, interpersonal skills, and physiological function, in individuals with autism. OBJECTIVES: To determine the efficacy of vitamin B6 and magnesium (B6-Mg) for treating social, communication, and behavioural responses of children and adults with autism. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), MEDLINE (1966 to January 2002), EMBASE (1980 to January 2002), PsycINFO (1887 to January 2002), Dissertation Abstracts International (1861 to January 2002). The search engine FirstSearch was also used (January 2002). All searches were updated in April 2005. Reference lists for all the obtained studies and other review articles were examined for additional studies. SELECTION CRITERIA: All studies in which the participants had been diagnosed with autistic spectrum disorder were randomly allocated prior to intervention and in which outcomes were compared to either a placebo or non-treated group were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated and extracted data from all potential studies identified for inclusion. MAIN RESULTS: This update includes a new trial (Kuriyama 2002) to bring the total of included studies to three (total n=33). One study, which used a cross-over design (Tolbert 1993) provided insufficient data to conduct an analysis. Another crossover study (Findling 1997) yielded no significant differences between treatment and placebo group performances following the B6 intervention on measures of social interaction, communication, compulsivity, impulsivity, or hyperactivity. The latest study (Kuriyama 2002) was motivated by evidence from epilepsy research and was focussed on a subgroup of children with pervasive developmental disorders (PDDs) who exhibited clinical features similar to those with pyroxidine-dependent epilepsy. This small study (n=8) only measured IQ and 'Social Quotient' and found a statistically significant benefit for IQ (5.2, 95% CI = [0.2 to 10.3]) when in the treated group, by using change scores. AUTHORS' CONCLUSIONS: Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism.

Witelo--Polish vision scientist of the middle ages: father of physiological optics.

Unknown to the Western hemisphere, a Polish scientist, naturalist, anatomist, physiologist, philosopher and optician, Witelo, wrote an important ten volume manuscript, Peri-Optikes, usually cited in the literature as Perspectiva. This classic textbook was first published in 1535 in Nuremberg under the title: Vitellionis mathematici doctissimi ... vulgo Perspectivam vocant libri X, which is translated to English as Perspectiva. It was a vital source of information for such scientists as Leonardo da Vinci, Keppler and others in the next few centuries. Although many of his ideas were similar to Alhazan's, who earlier had written a significant optical manuscript De aspectibus, Witelo developed his own interpretation of many optical issues. He was one of the first scientists to discover spherical aberration of concave lenses and concave mirrors. He was also first to point out "that deflection of the light ray increases with the angle in which they approach two different optical substances and each increase is smaller than the previous one." Until recently, Witelo's achievements and contributions to the understanding of optical and anatomical aspects of the eye and visual function have remained unknown in western literature. Undoubtedly, Witelo should be recognized as the father of physiological optics.

Coping with oral surgery by self-efficacy enhancement and perceptions of control.

Recent work has suggested that patients' coping could be improved in stressful dental situations if perceptions of self-efficacy and control could be enhanced. To test this hypothesis, 70 first-time third-molar extraction patients were randomly assigned to one of four surgery preparation conditions: standard preparation, oral premedication, relaxation, and a relaxation+efficacy-enhancing feed-back condition in which subjects were given false galvanic skin response (GSR) biofeedback leading them to believe that they were highly skilled at relaxing. Analyses indicated that: (1) all treatments were seen as equally credible (controlling for placebo effects); (2) a priori contrasts showed that both the relaxation-only treatment and the relaxation+efficacy-enhancement treatment were superior to the premedication and standard preparations in raising coping self-efficacy; (3) regardless of treatment condition, increase in reported coping self-efficacy was significantly correlated with pre-operative anxiety, with self-reported peri-operative distress, and with behavioral ratings of peri-operative distress; and (4) the relaxation treatments resulted in lower pre-operative anxiety than the other interventions, and linear contrasts showed significant trends in which the relaxation+efficacy-enhancing condition was superior to the relaxation-only condition, which was in turn superior to the medication condition and the standard preparation in reducing both pre-operative anxiety and behavioral ratings of peri-operative distress. It was concluded that thoughts related to self-confidence and control can be manipulated, and that these thoughts can in part determine how well a person copes in stressful dental situations.

Early intervention in the path to alcohol problems through conduct problems: treatment involvement and child behavior change.

A program for the prevention of conduct problems among preschool-age sons of alcoholic fathers was implemented to interrupt what is likely to be a major mediating factor in the development of alcoholism in later years. A population-based sample of 42 families participated in a 10-month intervention involving parent training and marital problem solving. Differences in treatment outcome were examined, with the expectation that level of treatment involvement--entailing both level of participation and level of investment--would account for variability in child outcome at termination. Significant changes in positive and negative child behaviors were observed only within the group of families who completed the program and where the mothers demonstrated a higher level of treatment investment. When pretreatment child, parent, and family predictors of child behavior change were accounted for, subsequent analyses identified maternal treatment investment as a significant predictor of child outcome.

Early family-based intervention in the path to alcohol problems: rationale and relationship between treatment process characteristics and child and parenting outcomes.

OBJECTIVE: Risk for subsequent development of alcohol problems is not uniform across the population of alcoholic families, but varies with parental comorbidity and family history. Recent studies have also identified disruptive child behavior problems in the preschool years as predictive of alcoholism in adulthood. Given the quality of risk structure in highest risk families, prevention programming is more appropriately family based rather than individual. METHOD: A family-based intervention program for the prevention of conduct problems among preschool-age sons of alcoholic fathers was implemented to change this potential mediating risk structure. A population-based recruitment strategy enrolled 52 alcoholic families in a 10-month intervention involving parent training and marital problem solving. The study examined the interplay between parent treatment investment and parent and therapist expectations and satisfaction in predicting change in child behavior and authoritative parenting style during the program, and for 6 months afterward among the 29 families whose sustained involvement allowed these effects to be evaluated. RESULTS: Parent expectations at pretreatment influenced their early investment in the program, which in turn predicted child and parenting outcomes. Parent and therapist satisfaction ratings during treatment were associated with one another and with expectations that the program would continue to promote changes in their child. Parent investment was a particularly salient influence on outcome, as higher investment throughout the program was associated with improvement in child behavior and authoritative parenting at termination. CONCLUSIONS: Findings indicate that treatment process characteristics mediate the influence of baseline parent functioning on treatment success and that treatment changes themselves predict later child outcomes.

Combined vitamin B6-magnesium treatment in autism spectrum disorder.

BACKGROUND: The use of mega-vitamin intervention began in the early 1950's with the treatment of schizophrenic patients. Pyroxidine (vitamin B6) was first used with children diagnosed with "autism syndrome" when speech and language improvement was observed in some children as a result of large doses of B6. A number of published studies attempted to assess the effects of vitamin B6-Mg (Mg was found to reduce undesirable side effects from B6) on a variety of characteristics such as verbal communication, non-verbal communication, interpersonal skills, and physiological function, in individuals with autism. OBJECTIVES: To determine the efficacy of vitamin B6 and magnesium (B6-Mg) for treating social, communication and behavioural responses of children and adults with autism. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), MEDLINE (1966- January 2002), EMBASE (1980-January 2002), PsychINFO (1887 - January 2002), Dissertation Abstracts International (1861 - January 2002). The search engine FirstSearch was also used (January 2002). Reference lists for all the obtained studies and other review articles were examined for additional studies. SELECTION CRITERIA: All studies in which the participants were randomly allocated prior to intervention and in which outcomes were compared to either a placebo or non-treated group were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated all potential studies identified as indicated above for inclusion. MAIN RESULTS: Two trials were included in the review. Both studies used a double-blind crossover design. One study (Tolbert 1993) provided insufficient data to conduct an analysis. The senior author was contacted for supporting data but was unable to provide the needed information. The remaining study (Findling, 1997) yielded no significant differences between treatment and placebo group performances following the B6 intervention on measures of social interaction, communication, compulsivity, impulsivity, or hyperactivity. REVIEWER'S CONCLUSIONS: Due to the small number of studies, the methodological quality of studies, and small sample sizes, no recommendation can be advanced regarding the use of B6-Mg as a treatment for autism.

Speech and language therapy interventions for children with primary speech and language delay or disorder.

BACKGROUND: It is thought that approximately 6% of children have speech and language difficulties of which the majority will not have any other significant developmental difficulties. Whilst most children's difficulties resolve, children whose difficulties persist into primary school may have long-term problems concerning literacy, socialisation, behaviour and school attainment. OBJECTIVES: To examine the effectiveness of speech and language interventions for children with primary speech and language delay/disorder. SEARCH STRATEGY: The following databases were searched: The Cochrane Controlled Trials Register (Cochrane Library, CENTRAL: 2002/3), CINAHL (1982 - July 2002), EMBASE (1980 - Sept Week 4 2002), ERIC (1965 - 2002), MEDLINE (1966 - Sept Week 3 2002), PsycINFO (1872 - 2002/10 Week 2), The National Research Register (2002/3). In addition to this references were taken from reviews of the literature and reference lists from articles. SELECTION CRITERIA: The review considered randomised controlled trials of speech and language therapy interventions for children or adolescents with primary speech and language delay/disorder. DATA COLLECTION AND ANALYSIS: Titles and abstracts were identified and assessed for relevance, before the full text version was obtained of all potentially relevant articles. The data were categorised depending on the nature of the control group and considered in terms of the effects of intervention on expressive and receptive phonology, syntax and vocabulary. The outcomes used in the analysis were dependent on the focus of the study with only the primary effects of therapy being considered in this review. MAIN RESULTS: The results of twenty-five studies were used in the meta-analysis. The results suggest that speech and language therapy is effective for children with phonological (SMD=0.44, 95%CI: 0.01,0.86) or vocabulary difficulties (SMD=0.89, 95%CI: 0.21,1.56), but that there is less evidence that interventions are effective for children with receptive difficulties (SMD=-0.04, 95%CI: -0.64,0.56). Mixed findings were found concerning the effectiveness of expressive syntax interventions (n=233; SMD=1.02, 95%CI: 0.04-2.01). No significant differences were shown between clinician administered intervention and intervention implemented by trained parents, and studies did not show a difference between the effects of group and individual interventions (SMD=0.01, 95%CI: -0.26,1.17). The use of normal language peers in therapy was shown to have a positive effect on therapy outcome (SMD=2.29, 95%CI: 1.11,3.48). REVIEWER'S CONCLUSIONS: The review shows that overall there is a positive effect of speech and language therapy interventions for children with expressive phonological and expressive vocabulary difficulties. The evidence for expressive syntax difficulties is more mixed, and there is a need for further research to investigate intervention for receptive language difficulties. There is a large degree of heterogeneity in the results, and the sources of this need to be investigated.

Botulinum toxin injections for the treatment of spasmodic dysphonia.

BACKGROUND: The use of botulinum toxin for the treatment of spasmodic dysphonia is currently the treatment of choice for management of this neurological voice disorder. Over the past 20 years, botulinum toxin has been used to treat both adductor and abductor forms of the disorder, with vocal improvement noted after treatment for both. A large number of studies have attempted to document the efficacy of botulinum toxin for improvement of vocal symptoms in individuals with spasmodic dysphonia. OBJECTIVES: To determine the effectiveness of botulinum toxin for treating spasmodic dysphonia. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to July 2003), EMBASE (1974 to July 2003 ), CINAHL (through July 2003), Dissertation Abstracts International (1975 to July 2003) and PsycINFO (1975 to July 2003). The search engine FirstSearch was also used (July 2003). Reference lists for all the obtained studies and other review articles were examined for additional studies. SELECTION CRITERIA: All studies in which the participants were randomly allocated prior to intervention and in which botulinum toxin was compared to either an alternative treatment, placebo or non-treated control group were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated all potential studies meeting the selection criteria noted above for inclusion. One study met the inclusion criteria and was included in the final analysis. MAIN RESULTS: Only one study in the literature met the inclusion criteria. This was the only study identified which reported a treatment/no treatment comparison. It reported significant beneficial effects for fundamental frequency (Fo), Fo Range, spectrographic analysis, independent ratings of voice severity and patient ratings of voice improvement. REVIEWERS' CONCLUSIONS: The evidence from randomized controlled trials does not allow firm conclusions to be drawn about the effectiveness of botulinum toxin for all types of spasmodic dysphonia, or for patients with different behavioral or clinical characteristics.

The utility of meta-analysis in the determination of efficacy of treatment in aphasia: a reply to Robey (1994).

In response to Robey (1994) we argue that his judgment of our study and conclusions (Whurr, Lorch, & Nye, 1992) are inaccurate. We point out that our study was in fact an analysis of the effects of treatment for aphasic patients. Further, the results obtained in Robey's analysis, though obtained via a different strategy of analysis, yielded essentially the same degree of overall treatment outcome effect. Thus, we conclude that while Robey does provide a different model of effect size data organization and measurement, the results are no different and do not in fact contradict our data.

Intraocular pressure, anterior chamber depth and axial length following intravenous mannitol.

The intraocular pressure (IOP), anterior chamber depth (ACD), and axial length (AL) were measured in 38 eyes of 19 subjects before and after intravenous mannitol injection (12.5 g). Intraocular pressures dropped over the initial 30 min then rose back to baseline by 2 hr. Time 0 min:14.2 mmHg, 15 min:12.7 mmHg, 30 min:11.4 mmHg, 60 min:12.0 mmHg, 90 min, 13.2 mmHg, 120 min:14.1 mmHg. Sitting and supine ACD and AL did not change following mannitol injection. This study supports an ocular hypotensive effect of mannitol without reducing vitreous volume using a relatively low dose of mannitol (12.5 g). This finding has important implications for its use in ocular surgery at this dosage.

Acoustic characteristics of children who speak Arabic.

The vocal characteristics of mean fundamental frequency, jitter, shimmer, harmonics-to-noise ratio, and breathiness were analyzed in 110 (F = 54, M = 56) Arabic-speaking children. The subjects were from Amman, Jordan, ranging in age from 5 to 20 years. Each subject was tape recorded during the production of the vowels /a/ and /i/. Two second samples of each vowel were analyzed using GW Instrument's Sound Scope software program. Means, standard deviations, and ranges were obtained and summarized for the acoustic measures in each age and gender category.

Effects of systemic and lateral semicircular canal administration of aminoglycosides on normal and hydropic inner ears.

Streptomycin was injected subcutaneously into guinea pigs (n = 12) with unilateral endolymphatic hydrops. In the unoperated ears, sensory cells were degenerated at the basal ends of all cochleas and to varying extents in the vestibular sense organs. Hydropic ears, in contrast, showed greater ototoxicity in the cochlear and saccular sensory cells, while the drug's effect on the utricular and cristae sensory cells was increased, but less remarkable. In another series of normal animals (n = 16), streptomycin was applied to a fenestra of the lateral semicircular canal. Sensory cells of all three canal cristae and utricular macula were degenerated frequently, but the sensory cells of the cochleas were rarely affected. The vestibular lesions resulting from the canal approach were greater than those produced by systemic injection. Comparison with a former gentamicin-lateral canal series revealed very little difference in action of the two drugs. However, in hydropic ears, gentamicin application to the lateral canal produced increased lesions in all sensory cells, particularly in the organ of Corti. Hydropic ears are vulnerable and a greater caution is needed in administering aminoglycosides by both the systemic and the canal route to patients with Meniere's disease.

Evidence for the effectiveness of botulinum toxin for spasmodic dysphonia from high-quality research designs.

The practice of evidence-based medicine promotes use of the knowledge ascertained from high quality research designs. The objective of this review was to determine what evidence has been provided from high quality research designs (e.g., randomized control trials or high quality prospective, matched group cohort studies), through December of 2006, relative to the effectiveness of botulinum toxin for treating spasmodic dysphonia. Results of the review indicated that no new high quality (Class I or Class II) studies have been published since 2001. One Class I study has been published since 1973, which found significant treatment effects for acoustic and perceptual variables of vocal function. Four Class II studies have been published during this same time frame, all finding significant treatment effects, though the nature of studied factors was variable between investigations. Based on the quality of evidence scale used, botulinum toxin can be considered an effective treatment for adductor spasmodic dysphonia.