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Recent years have witnessed increased antipsychotic treatment of children despite limited long‐term safety data in children. In this study, motor side effects associated with the use of antipsychotic drugs in children were examined in a sample of pediatric psychiatric patients. Child and adolescent psychiatric patients receiving antipsychotics (most were on atypicals) for 6 months or longer (n = 118) were compared with antipsychotic‐naïve patients (n = 80) with similar age, sex ratio, and diagnoses. Only 19% of patients on antipsychotics had ever experienced psychotic symptoms. Eleven children (9%) on antipsychotics exhibited dyskinesia, when compared with 0 in the naïve group (P = 0.003, Fisher's exact test). Nine of 62 African–American children (15%) on antipsychotics exhibited dyskinesia, when compared with only 4% (2 of 52) of European–American children (P = 0.003, Fisher's exact test). Children treated with antipsychotic drugs might experience a significant risk of dyskinesia even when treated only with atypical antipsychotics. Ethnicity might also be a risk factor for dyskinesia in children. Side‐effect profile of the atypical antipsychotic drugs in children may be much different than that in adults. © 2007 Movement Disorder Society  相似文献   
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Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.  相似文献   
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Cobalt is a toxic metal used in various industrial applications leading to adverse lung effects by inhalation. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt‐induced toxicity in human lung cells, especially normal lung epithelial cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in normal primary human lung epithelial cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration‐dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble and particulate cobalt induced similar cytotoxicity while soluble cobalt was more genotoxic than particulate cobalt. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung epithelial cells. Environ. Mol. Mutagen. 57:282–287, 2016. © 2016 Wiley Periodicals, Inc.  相似文献   
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Background

Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality. Genetic heart diseases (GHDs) underlie some cases of SIDS.

Objectives

This study aimed to determine the spectrum and prevalence of GHD-associated mutations as a potential monogenic basis for SIDS.

Methods

A cohort of 419 unrelated SIDS cases (257 male; average age 2.7 ± 1.9 months) underwent whole exome sequencing and a targeted analysis of 90 GHD-susceptibility genes. The yield of “potentially informative,” ultra-rare variants (minor allele frequency <0.00005) in GHD-associated genes was assessed.

Results

Overall, 53 of 419 (12.6%) SIDS cases had ≥1 “potentially informative,” GHD-associated variant. The yield was 14.9% (21 of 141) for mixed-European ancestry cases and 11.5% (32 of 278) for European ancestry SIDS cases. Infants older than 4 months were more likely to host a “potentially informative” GHD-associated variant. There was significant overrepresentation of ultra-rare nonsynonymous variants in European SIDS cases (18 of 278 [6.5%]) versus European control subjects (30 of 973 [3.1%]; p = 0.013) when combining all 4 major cardiac channelopathy genes (KCNQ1, KCNH2, SCN5A, and RYR2). According to the American College of Medical Genetics guidelines, only 18 of 419 (4.3%) SIDS cases hosted a “pathogenic” or “likely pathogenic” variant.

Conclusions

Less than 15% of more than 400 SIDS cases had a “potentially informative” variant in a GHD-susceptibility gene, predominantly in the 4- to 12-month age group. Only 4.3% of cases possessed immediately clinically actionable variants. Consistent with previous studies, ultra-rare, nonsynonymous variants within the major cardiac channelopathy-associated genes were overrepresented in SIDS cases in infants of European ethnicity. These findings have major implications for the investigation of SIDS cases and families.  相似文献   
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Objective. To design and assess a horizontally integrated biological sciences course sequence and to determine its effectiveness in imparting the foundational science knowledge necessary to successfully progress through the pharmacy school curriculum and produce competent pharmacy school graduates.Design. A 2-semester course sequence integrated principles from several basic science disciplines: biochemistry, molecular biology, cellular biology, anatomy, physiology, and pathophysiology. Each is a 5-credit course taught 5 days per week, with 50-minute class periods.Assessment. Achievement of outcomes was determined with course examinations, student lecture, and an annual skills mastery assessment. The North American Pharmacist Licensure Examination (NAPLEX) results were used as an indicator of competency to practice pharmacy.Conclusion. Students achieved course objectives and program level outcomes. The biological sciences integrated course sequence was successful in providing students with foundational basic science knowledge required to progress through the pharmacy program and to pass the NAPLEX. The percentage of the school’s students who passed the NAPLEX was not statistically different from the national percentage.  相似文献   
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Background

Despite high rates of women''s use of intrapartum pain management techniques, little is known about the factors that influence such use.

Objective

Examine the determinants associated with women''s use of labour pain management.

Design

Cross‐sectional survey of a substudy of women from the ‘young’ cohort of the Australian Longitudinal Study of Women''s Health (ALSWH).

Setting and participants

Women aged 31–35 years who identified as being pregnant or recently given birth in the 2009 ALSWH survey (n = 2445) were recruited for the substudy. The substudy survey was completed by 1835 women (RR = 79.2%).

Main variables studied

Determinants examined included pregnancy health and maternity care [including complementary and alternative medicine (CAM)] for their most recent pregnancy and any previous pregnancies. Participants'' attitudes and beliefs related to both CAM and maternity care were also included in the analysis.

Main outcome measures

The outcome measures examined were the use of both pharmacological and non‐pharmacological pain management techniques (NPMT).

Results

Differences were seen in the effects of demographics, health service utilization, health status, use of CAM, and attitudes and beliefs upon use of intrapartum pain management techniques across all categories. The only variable that was identified as a determinant for use of all types of pain management techniques was a previous caesarean section (CS).

Discussion and conclusions

The effect of key determinants on women''s use of pain management techniques differs significantly, and, other than CS, no one determinant is clearly influential in the use of all pain management options.  相似文献   
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BackgroundIntranasal ketorolac has been proposed as a diagnostic test for aspirin-exacerbated respiratory disease (AERD) and a faster, safer, and reliable addition to facilitating aspirin (ASA) desensitization.ObjectiveWe conducted the first prospective study to dissect the impact of intranasal ketorolac incorporation during ASA desensitization vs standard oral protocols in concert with evaluating its diagnostic use for AERD.MethodsPatients with AERD were enrolled in a prospective open-label observational study between November 2006 and August 2013. Participants selected either one of the following desensitization protocols: intranasal ketorolac 1 day before oral ASA (group 1, combined) or ketorolac challenge with greater than 2 weeks elapsing until oral ASA (group 2, washout). All patients were on a leukotriene-modifying drug (montelukast) for at least 1 week before the challenge.ResultsA total of 20 patients were enrolled: 13 in group 1 and 7 in group 2. No significant differences were seen for baseline symptom scores or forced expiratory volume in 1 second. Group 1 exhibited significant increases for the threshold dose of ASA (P = .009), the likelihood of having silent ASA desensitization (P = .01), and decreased reaction severity to oral ASA (P = .04). There were no significant differences in reaction forced expiratory volume in 1 second, the incidence of extrapulmonary symptoms, limited nasoocular reactions, rescue treatment requirements, or time to symptom resolution. There was 100% concordance between reactions to intranasal ketorolac and oral ASA for group 2, supporting its use as a diagnostic test for AERD.ConclusionIntranasal ketorolac is a useful diagnostic test and adjunct within the combined ketorolac/ASA protocol to achieve effective, efficient, and perhaps safer desensitization to ASA for patients with AERD.  相似文献   
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