Using embedded music therapy interventions to support outdoor play of young children with autism in an inclusive community-based child care program

For young children with autism enrolled in community-based inclusive child care programs, outdoor play can be a major challenge. The aim of this music therapy intervention was to improve peer interactions and meaningful play on the playground for four boys with autism by adding an outdoor music center and using original songs composed for each participant. A collaborative approach was used to support the implementation of the intervention by the children's teachers, engaging classroom peers as formal and informal helpers. The effects of the interventions were examined using a multiple baseline design with four conditions replicated across the four children. The results indicate that the musical adaptation of the playground itself did not improve social interactions of children with autism significantly, but it facilitated their play and involvement with peers by attraction to the sound and opportunity to use the instruments. The song interventions produced desirable peer interaction outcomes, and the collaborative consultative approach enabled teachers to implement interventions successfully in ongoing playground routines. In addition, peer-mediated strategies increased peer interactions and meaningful play on the playground.     

Cardiocerebral resuscitation for cardiac arrest

Survival rates from out-of-hospital cardiac arrest continue to be low despite periodic updates in the Guidelines for Emergency Medical Services and periodic improvements such as the addition of automatic external defibrillators (AEDs). The low incidence of bystander cardiopulmonary resuscitation (CPR), substantial time without chest compressions throughout the resuscitation effort, and a lack of response to initial defibrillation after prolonged ventricular fibrillation contribute to these unacceptably poor results. Resuscitation guidelines are only revised every 5 to 7 years and can be difficult to change because of the lack of randomized controlled trials in humans. Such trials are rare because of a number of logistical difficulties, including the problem of obtaining informed consent. An alternative approach to advancing resuscitation science is for evidence-based demonstration projects in areas that have adequate records, so that one may determine whether the new approach improves survival. This is reasonable because the current guidelines make provisions for deviations under certain local circumstances or as directed by the emergency medical services medical director. A wealth of experimental evidence indicates that interruption of chest compressions for any reason in patients with cardiac arrest is deleterious. Accordingly, a new approach to out-of-hospital cardiac arrest called cardiocerebral resuscitation (CCR) was developed that places more emphasis on chest compressions for witnessed cardiac arrest in adults and de-emphasizes ventilation. There is also emphasis on chest compressions before defibrillation in circulatory phase of cardiac arrest. CCR was initiated in Tucson, Arizona, in November 2003, and in two rural Wisconsin counties in early 2004.     

Physiological assessment of coronary artery disease in the cardiac catheterization laboratory: a scientific statement from the American Heart Association Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology

With advances in technology, the physiological assessment of coronary artery disease in patients in the catheterization laboratory has become increasingly important in both clinical and research applications, but this assessment has evolved without standard nomenclature or techniques of data acquisition and measurement. Some questions regarding the interpretation, application, and outcome related to the results also remain unanswered. Accordingly, this consensus statement was designed to provide the background and evidence about physiological measurements and to describe standard methods for data acquisition and interpretation. The most common uses and support data from numerous clinical studies for the physiological assessment of coronary artery disease in the cardiac catheterization laboratory are reviewed. The goal of this statement is to provide a logical approach to the use of coronary physiological measurements in the catheterization lab to assist both clinicians and investigators in improving patient care.     

Targeted disruption of FANCC and FANCG in human cancer provides a preclinical model for specific therapeutic options

BACKGROUND & AIMS: How specifically to treat pancreatic and other cancers harboring Fanconi anemia gene mutations has raised great interest recently, yet preclinical studies have been hampered by the lack of well-controlled human cancer models. METHODS: We endogenously disrupted FANCC and FANCG in a human adenocarcinoma cell line and determined the impact of these genes on drug sensitivity, irradiation sensitivity, and genome maintenance. RESULTS: FANCC and FANCG disruption abrogated FANCD2 monoubiquitination, confirming an impaired Fanconi anemia pathway function. On treatment with DNA interstrand-cross-linking agents, FANCC and FANCG disruption caused increased clastogenic damage, G2/M arrest, and decreased proliferation. The extent of hypersensitivity varied among agents, with ratios of inhibitory concentration 50% ranging from 2-fold for oxaliplatin to 14-fold for melphalan, a drug infrequently used in solid tumors. No hypersensitivity was observed on gemcitabine, etoposide, 3-aminobenzamide, NU1025, or hydrogen peroxide. FANCC and FANCG disruption also resulted in increased clastogenic damage on irradiation, but only FANCG disruption caused a subsequent decrease in relative survival. Finally, FANCC and FANCG disruption increased spontaneous chromosomal breakage, supporting the role of these genes in genome maintenance and likely explaining why they are mutated in sporadic cancer. CONCLUSIONS: Our human cancer cell model provides optimal controls to elucidate fundamental biologic features of individual Fanconi anemia gene defects and facilitates preclinical studies of therapeutic options. The impact of Fanconi gene defects on drug and irradiation sensitivity renders these genes promising targets for a specific, genotype-based therapy for individual cancer patients, providing a strong rationale for clinical trials.     

Effects of simultaneous application of ultrasound and microbubbles on intracerebral hemorrhage in an animal model

Microbubble-enhanced sonothrombolysis (MEST) may be an alternative therapeutic option in ischemic stroke. Clinical study of the efficacy of MEST as an adjunct stroke therapy, before imaging with CT or MRI, requires experimental data on the safety of this approach in the presence of hemorrhagic stroke. We, therefore, investigated the effect of diagnostic transcranial ultrasound combined with microbubbles (US + MB) in an experimental animal model of intracerebral hemorrhage (ICH). ICH was induced in anesthetized rats by intracerebral collagenase injection. Transcranial ultrasound (2 MHz, mechanical index 1.3, 1051 kPa) was applied 3 h after ICH induction to rat brains for 30 min during a continuous IV infusion of sulfur hexafluoride microbubbles (SonoVue). The size of cerebral hemorrhage, the extent of brain edema, and the amount of apoptosis were compared with those from control rats with ICH but without US + MB. Results showed no significant effect of US + MB on hemorrhage size (control 23.3 +/- 10.7 mm(3), US + MB 20.3 +/- 5.8 mm(3)), on the extent of brain edema (control 3.3 +/- 2.0%, US +MB 3.5 +/- 1.9%), or on the rate of apoptosis (control 5.2 +/- 1.5%, US + MB 5.2 +/- 1.0%). We conclude that diagnostic ultrasound in combination with microbubbles does not cause additional damage to the rat brain during ICH in our experimental set-up. This finding provides support for the use of MEST as an early stroke therapy.     

Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Escherichia coli

OBJECTIVES: 1-(1-Naphthylmethyl)-piperazine (NMP) has been shown to reverse multidrug resistance (MDR) in Escherichia coli overexpressing resistance-nodulation-cell division type efflux pumps, but there is no data on its activity in clinical isolates of E. coli. METHODS: The antimicrobial susceptibility of 60 clinical isolates of E. coli to a variety of antimicrobial agents was determined in the absence and presence of NMP and, for comparison, of Phe-Arg-beta-naphthylamide (PAbetaN), another putative efflux pump inhibitor (EPI). The intracellular accumulation of ethidium bromide was measured to confirm efflux pump inhibition as the likely mechanism of action of NMP. RESULTS: Based on a 4-fold or greater reduction of the MIC after the addition of NMP in >50% of the isolates, significant effects of NMP at a concentration of 100 mg/L were seen for levofloxacin, linezolid and ethidium bromide. The ethidium bromide MIC changes after NMP addition correlated with differences in the ethidium bromide intracellular accumulation as measured by fluorometry in whole cell accumulation experiments. The activity of PAbetaN was different from that of NMP, in particular regarding macrolide resistance reversal, suggesting different modes of action of the two putative EPIs. CONCLUSIONS: NMP is moderately active in reversing MDR in clinical isolates of E. coli and can partially restore fluoroquinolone susceptibility through inhibition of efflux pumps.     

Subjective and objective perception of upper incisors

The purpose of this study was to evaluate the subjective judgment (SJ) of patients on their own dental appearance and to correlate the results with objective measurements (OM) of their dentition concerning the appearance of the upper incisors. Seventy-five participants (30 men and 45 women) with normal well-being were included in the study. In a questionnaire they judged the appearance of their upper incisors. Furthermore, OM were evaluated by the investigator with regard to the following points: (i) absolute length of the upper central incisors, (ii) their length exposed during laughing, (iii) width-to-length ratio of central incisors and (iv) the proportion between the width of the lateral and central incisors. The subjective results were registered on visual-analogue scales. For the objective results standardized photographs were taken. No gender dependent differences could be found for the objectively measured parameters (median): OM1, 10.7 mm; OM2, 8.1 mm; OM3, 0.81; OM4, 0.79. However, significant correlations between subjective and objective results (SJ1/OM1, SJ2/OM2, SJ3/OM3) could be shown for men, but not for women. The maximum of the calculated regression-curves for men reflect 'golden standard values' well known from the literature. The degree of satisfaction concerning appearance of anterior incisors in accordance with golden standard values is higher for men than for women.     

Interpreting hair mercury levels in individual patients

Evaluation of mercury exposure in an individual patient ideally includes the presenting history, physical examination, consideration of the differential diagnosis, and mercury analysis of blood and urine specimens. Analysis of mercury in hair specimens may supply useful supplemental information about exposure to organic compounds such as methylmercury, particularly to help reconstruct the pattern of prior exposure. The most appropriate specimen is generally terminal-type hair from the occipital-neck junction, clamped to maintain strand alignment, and oriented to the scalp. Hair from the initial 0.5 cm adjacent to the scalp represents on average 1-3 wk before collection, and consideration of the time frame represented by the specimen is an important part of the evaluation. Literature reports describe hair mercury levels as high as 2400 microg/g. Hair mercury level is usually <1 microg/g in individuals who do not eat fish but may be >30 microg/g in those who frequently consume fish with high mercury content. Hair mercury level is often not correlated with blood mercury concentration or symptoms of mercury toxicity, and reports of hair contamination by exogenous mercury are not uncommon. Hair mercury level is notoriously prone to misinterpretation and should be used with an understanding of its limitations.     

Gene expression patterns in peripheral blood cells associated with radiographic severity in African Americans with early rheumatoid arthritis

Gene expression profiling may be used to stratify patients by disease severity to test the hypothesis that variable disease outcome has a genetic component. In order to define unique expression signatures in African American rheumatoid arthritis (RA) patients with severe erosive disease, we undertook a gene expression study using samples of RNA from peripheral blood mononuclear cells (PBMCs). RNA from baseline PBMC samples of 96 African American RA patients with early RA (<2 years disease duration) was hybridized to cDNA probes of the Illumina Human HT-V3 expression array. Expression analyses were performed using the ca. 25,000 cDNA probes, and then expression levels were compared to the total number of erosions in radiographs of the hands and feet at baseline and 36 months. Using a false discovery rate cutoff of Q = 0.30, 1,138 genes at baseline and 680 genes at 36 months significantly correlated with total erosions. No evidence of a signal differentiating disease progression, or change in erosion scores between baseline and 36 months, was found. Further analyses demonstrated that the differential gene expression signature was localized to the patients with the most erosive disease (>10 erosions). Ingenuity Pathway Analysis demonstrated that genes with fold change greater than 1.5 implicated immune pathways such as CTLA signaling in cytotoxic T lymphocytes. These results demonstrate that CLEAR patients with early RA having the most severe erosive disease, as compared to more mild cases (<10 erosions), may be characterized by a set of differentially expressed genes that represent biological pathways with relevance to autoimmune disease.