Validation of a quantitative NMR method for suspected counterfeit products exemplified on determination of benzethonium chloride in grapefruit seed extracts

A 1H-nuclear magnetic resonance (NMR) spectroscopy method for quantitative determination of benzethonium chloride (BTC) as a constituent of grapefruit seed extract was developed. The method was validated, assessing its specificity, linearity, range, and precision, as well as accuracy, limit of quantification and robustness. The method includes quantification using an internal reference standard, 1,3,5-trimethoxybenzene, and regarded as simple, rapid, and easy to implement. A commercial grapefruit seed extract was studied and the experiments were performed on spectrometers operating at two different fields, 300 and 600 MHz for proton frequencies, the former with a broad band (BB) probe and the latter equipped with both a BB probe and a CryoProbe. The concentration average for the product sample was 78.0, 77.8 and 78.4 mg/ml using the 300 BB probe, the 600MHz BB probe and CryoProbe, respectively. The standard deviation and relative standard deviation (R.S.D., in parenthesis) for the average concentrations was 0.2 (0.3%), 0.3 (0.4%) and 0.3mg/ml (0.4%), respectively.     

Spondyloenchondrodysplasia Due to Mutations in <Emphasis Type="Italic">ACP5</Emphasis>: A Comprehensive Survey

Purpose

Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases.

Methods

We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations.

Results

We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy.

Conclusions

Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia.

     

Seasonal and weather variation of sleep and physical activity in 12–14-year-old children

Background: Understanding variation in physical activity (PA) and sleep is necessary to develop novel intervention strategies targeting adolescents’ health behaviors. We examined the extent to which PA and sleep vary by aspects of the physical environment. Participants: We performed a cross-sectional analysis of 669 adolescents in the Project Viva cohort. Methods: We estimated total PA, sleep duration, sleep efficiency, and sleep midpoint timing from wrist accelerometers. We used multivariable linear regression models and generalized estimated equations to assess associations of PA and sleep with season and daily weather conditions obtained from the National Oceanic and Atmospheric Administration archive. Results: Mean age was 12.9 (SD 0.6) years; 51% were female and 68% were white. Mean sleep duration was 466 (SD 42) min per night and total PA was 1,652 (SD 431) counts per min per day. Sleep midpoint time was 41 (95% CI: 27 to 54) min later in summer, 28 (95% CI: ?41 to ?14) min earlier in spring, and 29 (95% CI: ?43 to ?15) min earlier in autumn compared to winter. Higher temperature and longer day length both were associated with small reductions of nightly sleep duration. Adolescents were less physically active during winter and on rainy and short sunlight days. There was an inverse U-shaped relationship between PA and mean temperature. Conclusions: Season was associated with large changes in sleep timing, and smaller changes in other sleep and PA measurements. Given the importance of sleep and circadian alignment, future health behavioral interventions may benefit by targeting “season-specific” interventions.     

Upper airway dimensions in Class II malocclusion. Effects of headgear treatment

OBJECTIVE: To study the effects of cervical headgear treatment of Class II division 1 malocclusion on upper airway structures in children. MATERIALS AND METHODS: Forty children aged 9.1 (7.2-11.5) years with Class II division 1 malocclusion were treated using a cervical headgear as the only treatment appliance. The headgear consisted of a long outer bow bent 15 degrees upward and a large inner bow expanded 10 mm larger than the intermolar distance. Lateral cephalograms were taken before and after the treatment. Upper airway structures were estimated from the cephalograms. The results were compared to cross-sectional data of 80 age-matched controls with a Class I molar relationship. RESULTS: A Class I molar relationship was achieved in all treated children. The mean treatment time was 1.6 (0.3-3.1) years. The Class II malocclusion was accompanied by a similar or wider nasopharyngeal space than in the controls but narrower oro- and hypopharyngeal spaces. The retropalatal area was widened by the treatment (P < .05), whereas the rest of the oropharynx and hypopharynx remained narrower than in the controls. Before the treatment, the mandibular plane was in a more horizontal position than in the controls, but during the treatment, it rotated to a position similar to that of the controls. CONCLUSION: Class II division 1 malocclusion is associated with a narrower upper airway structure even without retrognathia. Headgear treatment is associated with an increase in the retropalatal airway space.     

Efficacy of Split Schedule Versus Conventional Schedule Neoadjuvant Cisplatin-Based Chemotherapy for Muscle-Invasive Bladder Cancer

Neoadjuvant cisplatin-based chemotherapy (NAC; 70 mg/m²) is standard of care for muscle-invasive bladder carcinoma (MIBC). Many patients (pts) cannot receive cisplatin because of renal impairment, and administration of cisplatin 35 mg/m² on day 1 + 8 or 1 + 2 (i.e., split schedule) is a commonly used alternative. In this retrospective analysis, we compared complete (pT0) and partial (<pT2) pathologic response rates between split schedule (SS) and conventional schedule (CS) pts, after 1:1 matching on chemotherapy regimen, number of cycles, tumor histology, and clinical stage. Eighty matched pts were identified. pT0 rates were 17.5% (95% confidence interval [CI], 7%–33%) and 32.5% (95% CI, 19%–49%) in SS and CS cisplatin pts, respectively (p = .21), corresponding to an odds ratio for pT0 of 0.45 (95% CI, 0.16–1.31) with SS cisplatin. Split schedule cisplatin was associated with numerically but not statistically significant lower pathologic response rates relative to full dose.