The factors which affect mid-facial growth in unilateral and bilateral cleft lip and palate

Aims To ascertain which factors influence mid-facial growth, when evaluated with the 5-year index. Method This was a retrospective cohort longitudinal study. One hundred and eighty-seven unilateral and bilateral cleft lip and palate patients that had undergone cleft lip and palate surgery, from 2000 to 2009, were included. There were two different but consistent techniques being used for the last 13 years. Factors investigated were surgical technique, severity of the cleft, anomalies of deciduous lateral incisors, and presence of bone in the cleft. Clinical notes, the cleft database, radiographs and dental study models were used. Comparisons were made using chi-squared tests at p<0.05. Results Technique B had significantly worse mid-facial growth for unilateral and bilateral cleft lip and palate patients (p<0.001; p=0.045) and a significantly higher number of cases with bone forming in the cleft (p=0.014; p=0.005). The severity of the cleft had a significant effect on the mid-facial growth (p=0.018; p=0.031). Anomalies of deciduous lateral incisors did not have a significant affect. A trend was present between the presence of bone and worse mid-facial growth. Conclusions Surgical technique, the severity of the cleft and the presence of bone have a significant effect on mid-facial growth

In vitro Characterization of Wild-type and Rifamycin-resistant Mycobacterium tuberculosis RNA polymerases.

Rifampin (a semi-synthetic rifamycin derivative) is one of the first-line anti-tuberculosis drugs. Rifampin inhibits transcription by binding to the beta-subunit of the RNA polymerase (RNAP). The majority of the clinically-relevant Mycobacterium tuberculosis (MTB) rifamycin-resistant (RifR) mutations result from amino acid substitutions of one of the following three beta residues: Asp435, His445, and Ser450 in a highly conserved 27 amino acid region of the RNAP beta-subunit. The core subunits of wild-type and RifR mutants (Asp435Val, His445Tyr, Ser450Leu) of MTB RNAP were overexpressed in and purified from E. coli. The rifamycins were all found to bind tightly (IC50) to the wild-type MTB and E. coli RNAPs, whereas dramatic (~10^2-10^5 fold) losses of affinity for rifamycins were observed for the RifR mutants from both bacteria. Additional studies with efflux pump-deficient E. coli (EC2880) confirm that the differential sensitivity of MTB and E. coli to rifamycin antibiotic activity is due to rifamycin efflux from E. coli, rather than any differences in the target RNAPs. The activities of C-8 modified rifamycins are consistent with X-ray crystal structures that show Ser450 acting as a hydrogen bond donor to the C-8 hydroxyl of rifamycins and that rifamycin resistance in the Ser450 mutants is likely due to loss of this hydrogen bond and loss of affinity. A series of novel benzoxazinorifamycin analogues displayed superior affinity toward wild-type and RifR mutants of the MTB RNAP than rifampin and rifalazil (RifR mutants, but not WT), but the IC50 values were still in the 10^-6 M range with the RifR MTB RNAPs. Rifampin exhibits significant drug-drug interactions via potent induction of cytochrome P450 3A4 (CYP3A4). Selected commercially available rifamycins and our synthetic analogues were screened in the human pregnane X receptor (hPXR) activation assay to determine their extents of hPXR activation as an indicator of potential for CYP3A4 induction. One of our analogues exhibited very low (similar to rifalazil) activation of hPXR, while the others did show significant activation and some cytotoxicity. The results of these studies have provided encouraging evidence that rifamycins with improved activity against RifR MTB RNAP and lower drug-drug interaction liabilities can be developed.PHDChemical BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/94011/1/sumankg_1.pd

Detection of volatile organic compounds in breath using thermal desorption electrospray ionization-ion mobility-mass spectrometry

A thermal desorption unit has been interfaced to an electrospray ionization-ion mobility-time-of-flight mass spectrometer. The interface was evaluated using a mixture of six model volatile organic compounds which showed detection limits of <1 ng sample loaded onto a thermal desorption tube packed with Tenax, equivalent to sampled concentrations of 4 μg L−1. Thermal desorption profiles were observed for all of the compounds, and ion mobility-mass spectrometry separations were used to resolve the probe compound responses from each other. The combination of temperature programmed thermal desorption and ion mobility improved the response of selected species against background ions. Analysis of breath samples resulted in the identification of breath metabolites, based on ion mobility and accurate mass measurement using siloxane peaks identified during the analysis as internal lockmasses

Alignment of retention time obtained from multicapillary column gas chromatography used for VOC analysis with ion mobility spectrometry

Multicapillary column (MCC) ion mobility spectrometers (IMS) are increasingly in demand for medical diagnosis, biological applications and process control. In a MCC-IMS, volatile compounds are differentiated by specific retention time and ion mobility when rapid preseparation techniques are applied, e.g. for the analysis of complex and humid samples. Therefore, high accuracy in the determination of both parameters is required for reliable identification of the signals. The retention time in the MCC is the subject of the present investigation because, for such columns, small deviations in temperature and flow velocity may cause significant changes in retention time. Therefore, a universal correction procedure would be a helpful tool to increase the accuracy of the data obtained from a gas-chromatographic preseparation. Although the effect of the carrier gas flow velocity and temperature on retention time is not linear, it could be demonstrated that a linear alignment can compensate for the changes in retention time due to common minor deviations of both the carrier gas flow velocity and the column temperature around the MCC-IMS standard operation conditions. Therefore, an effective linear alignment procedure for the correction of those deviations has been developed from the analyses of defined gas mixtures under various experimental conditions. This procedure was then applied to data sets generated from real breath analyses obtained in clinical studies using different instruments at different measuring sites for validation. The variation in the retention time of known signals, especially for compounds with higher retention times, was significantly improved. The alignment of the retention time—an indispensable procedure to achieve a more precise identification of analytes—using the proposed method reduces the random error caused by small accidental deviations in column temperature and flow velocity significantly

Bullying Victimization and Mental Health Outcomes of Sikh American Adolescents

Bullying victimization is a problem that permeates schools today, and the current literature base reveals an association between bullying victimization and negative mental health outcomes. Further, students of minority ethnic backgrounds (e.g., Asian American adolescents) have been shown to be at an increased risk of bullying victimization. This victimization based on ethnic group membership has been coined peer ethnic victimization. One group of students that are more at-risk for peer victimization is Sikh American adolescents, which may result from them being stereotyped as foreigners by others. The purpose of this study was to examine victimization and mental health outcomes in Sikh American adolescents. Structural equation modeling (SEM) was utilized to examine the relationships among wearing a religious head covering, being perceived as a foreigner, different types of victimization (i.e., physical, verbal, and relational) and mental health outcomes (i.e., self-esteem, depressive symptoms, and anxiety related to perceptions of school safety) for these students. The final model suggested that being perceived as a foreigner mediated the relationship between wearing a religious head covering and all three types of victimization, and that victimization mediated the relationship between being perceived as a foreigner and mental health outcomes. Implications for school psychologists are discussed