Social status and energy intake: a randomized controlled experiment.

While the inverse association between socioeconomic status (SES) and obesity in high gross domestic product countries is well established using observational data, the extent to which the association is due to a true causal effect of SES and, if so, the mechanisms of this effect remain incompletely known. To assess the influence of social status on obesity via energy intake, we randomized individuals to a higher or lower social status and observed subsequent energy intake. College students between the ages of 18 and 25 were randomized to social status and were operationalized as being a leader or follower in a partner activity as purportedly determined by a (bogus) test of leadership ability. Investigators were blinded to treatment assignment. Immediately after being told their leadership assignment, paired participants were provided with platters of food. Energy intake was objectively measured in kilocalories (kcal) consumed, and paired t-tests were used to test for significant differences in intake between leaders and followers. A total of 60 participants were included in the final analysis (males = 28, females = 32). Overall, no difference in energy intake was observed between leaders and followers, consuming an average of 575.3 and 579.8 kcal, respectively (diff = 4.5 kcal, P = 0.94). The null hypothesis of no effect of social status, operationalized as assignment to a leadership position in a small-group activity, on energy intake was not rejected.

Deficiency in myosin light-chain phosphorylation causes cytokinesis failure and multipolarity in cancer cells.

Cancer cells often have unstable genomes and increased centrosome and chromosome numbers, which are an important part of malignant transformation in the most recent model of tumorigenesis. However, very little is known about divisional failures in cancer cells that may lead to chromosomal and centrosomal amplifications. In this study, we show that cancer cells often failed at cytokinesis because of decreased phosphorylation of the myosin regulatory light chain (MLC), a key regulatory component of cortical contraction during division. Reduced MLC phosphorylation was associated with high expression of myosin phosphatase and/or reduced myosin light-chain kinase levels. Furthermore, expression of phosphomimetic MLC largely prevented cytokinesis failure in the tested cancer cells. When myosin light-chain phosphorylation was restored to normal levels by phosphatase knockdown, multinucleation and multipolar mitosis were markedly reduced, resulting in enhanced genome stabilization. Furthermore, both overexpression of myosin phosphatase or inhibition of the myosin light-chain kinase in nonmalignant cells could recapitulate some of the mitotic defects of cancer cells, including multinucleation and multipolar spindles, indicating that these changes are sufficient to reproduce the cytokinesis failures we see in cancer cells. These results for the first time define the molecular defects leading to divisional failure in cancer cells.

Atomoxetine treatment in children and adolescents with ADHD and comorbid tic disorders.

OBJECTIVE: To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid tic disorders. METHODS: Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks. RESULTS: Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures. CONCLUSIONS: Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.

Observer agreement in the grading of oral epithelial dysplasia.

OBJECTIVES: To determine the extent of observer agreement in diagnosis of oral epithelial dysplasia (OED). Published studies of OED examiner agreement report relatively low agreement levels; however, these studies were limited by the methodologies employed. METHODS: For this study, 64 slides were each independently examined twice by three oral pathologists. Consistency was assessed by determining intra- and interexaminer agreement. Conformity was assessed by using the modal diagnosis as a gold standard. RESULTS: The group showed moderate interobserver agreement when grading the presence or absence of OED with a group-simple kappa (Ks) of 0.51 (95% CI = 0.42-0.61), and substantial agreement when using a 5-point ordinal scale with a group-weighted kappa (Kw) of 0.74 (95% CI = 0.64-0.85). The group showed fair to substantial intraexaminer agreement when assessing the presence or absence of OED, with Ks ranging from 0.22 to 0.78, and showing almost a perfect agreement using a 5-point ordinal scale, with Kw ranging from 0.82-0.96. Conformity with the comparison standard modal diagnosis was almost perfect, with pairwise Kw ranging from 0.81 to 0.92. CONCLUSION: Overall, there was substantial intra- and interobserver consistency and almost perfect conformity in the grading of OED. Appropriate statistical methods are necessary to determine the degree of observer agreement.

Practice parameter: evaluation of children and adolescents with recurrent headaches: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

OBJECTIVE: The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. For this parameter, the authors reviewed available evidence on the evaluation of the child with recurrent headaches and made recommendations based on this evidence. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification. RESULTS: There is inadequate documentation in the literature to support any recommendation as to the appropriateness of routine laboratory studies or performance of lumbar puncture. EEG is not recommended in the routine evaluation, as it is unlikely to define or determine an etiology or distinguish migraine from other types of headaches. In those children undergoing evaluation for recurrent headache found to have a paroxysmal EEG, the risk for future seizures is negligible; therefore, further investigation for epilepsy or treatments aimed at preventing future seizures is not indicated. Obtaining a neuroimaging study on a routine basis is not indicated in children with recurrent headaches and a normal neurologic examination. Neuroimaging should be considered in children with an abnormal neurologic examination or other physical findings that suggest CNS disease. Variables that predicted the presence of a space-occupying lesion included 1) headache of less than 1-month duration; 2) absence of family history of migraine; 3) abnormal neurologic findings on examination; 4) gait abnormalities; and 5) occurrence of seizures. CONCLUSIONS: Recurrent headaches occur commonly in children and are diagnosed on a clinical basis rather than by any testing. The routine use of any diagnostic studies is not indicated when the clinical history has no associated risk factors and the child's examination is normal.

Solvent-free routes to clean technology.

A major aim for the chemical technology of the future is the avoidance of noxious and environmentally unacceptable organic solvents. In this concept article we discuss more environmentally friendly and highly selective alternatives which we have evolved for carrying out a number of important chemical conversions. These entail the use of porous heterogeneous catalysts in which the active sites have been atomically engineered and fully characterized. Such solid catalysts operate under solvent-free conditions and usually entail one-step processes.

Sites of conditional essential fatty acid deficiency in end stage liver disease.

BACKGROUND: End stage liver disease (ESLD) is a devastating illness. Its protean manifestations involve many different aspects of disturbed hepatic function. One consequence of ESLD is a decrease in plasma levels of very long chain polyunsaturated fatty acids (VL-PUFAs), particularly arachidonic acid (AA) and docosahexaenoic acid (DHA), the former important for eicosanoid metabolism and the latter for retinal and brain membrane structure. The purpose of this study was to define the VL-PUFA changes in liver disease by comparing plasma and tissue levels of VL-PUFAs in controls to patients with ESLD. METHODS: Fatty acid profiles from plasma, red blood cell (RBC) membranes, muscle, liver, and fat tissue from ESLD patients undergoing liver transplants were measured and compared with control patients undergoing elective liver resection. RESULTS: Fatty acid profiles from plasma and RBC membranes showed significant decreases in AA and DHA levels in patients with ESLD compared with controls. However, there were no significant differences in tissue fatty acid composition between ESLD patients and controls. CONCLUSIONS: ESLD affects the liver's ability to maintain circulating levels of AA and DHA, and thereby presumably RBC membrane levels. However, solid tissues appear not to be affected by ESLD. Although the mechanism for these changes remains to be defined, it is consistent with hepatic impairment of elongation and desaturation to produce VL-PUFA for transport. The present results also suggest that dietary interventions to include preformed VL-PUFA rather than their precursors, linoleic and alpha linolenic acid, would be needed to normalize plasma VL-PUFA levels in patients with ESLD.

Headache in the pediatric emergency department.

Headache is one of the most common presenting complaints to emergency departments. Although the overwhelming majority of these headaches are benign and self-limited, headache can be the initial symptom of life-threatening disorders. It is therefore essential for physicians to have a rational approach to the evaluation of a child or adolescent who presents to the emergency department with headache. The purpose of this article is to review the causes, evaluation, and appropriate investigations for nontraumatic headache in the pediatric emergency department.

The utility of neuroimaging in the evaluation of children with migraine or chronic daily headache who have normal neurological examinations.

OBJECTIVES: To assess the utility of neuroimaging in the evaluation of children presenting with two of the most common forms of headache, migraine and chronic daily headache, and to determine the utility and pathological yield of neuroimaging in specific headache syndromes in children whose neurological examinations are normal. METHODS: We retrospectively reviewed the medical records of patients coded for headache (ICD 784) in the Pediatric Neurology Clinic at Children's Hospital of the King's Daughters between 1997 and 1999. The age range considered was between 6 and 18 years. The study focused on the two most common types of headache, uncomplicated migraine and chronic daily headache. Only patients with normal physical and neurological examinations were considered in this analysis. RESULTS: Three hundred two patients were coded for headache within the defined age group. One hundred seven (35.4%) patients fulfilled IHS-R criteria as having uncomplicated migraine with a normal examination, and 30 (9.9%) patients fulfilled criteria for chronic daily headache. Twenty-nine (9.6%) patients presented with migrainelike symptoms, and 6 (2.0%) presented with chronic daily symptoms, but had neurological abnormalities present on examination. The remainder of the patients with headache had the following etiologies: 50 (16.6%) with secondary headache, 22 (7.3%) with complicated migraine, 20 (6.6%) with posttraumatic headache, 13 (4.3%) with seizure-related headache, 11 (3.6%) with brain tumors, 10 (3.3%) with tension-type headache, and 4 (1.3%) with pseudotumor cerebri. Of the 107 patients with migraine, 42 (39.3%) received CT scans; 2 (4.8%) of which were considered "abnormal." One of the abnormalities was an arachnoid cyst and the other was a dilated Virchow-Robin space. Twelve (11.2%) patients with migraine received an MRI, 2 (16.7%) of which were considered abnormal. Both of the abnormal findings were Chiari type I malformations. Of the 30 patients with chronic daily headache, 17 (56.7%) received CT scans, 3 (17.6%) of which were considered abnormal. The abnormalities consisted of a maxillary opacification, a mucous retention cyst, and an occult vascular malformation. Eight (26.7%) of the patients with chronic daily headache had an MRI, 2 (25.0%) of which were abnormal. One of the abnormalities was a Chiari I malformation, and the other was an occult vascular malformation. CONCLUSION: The yield of neuroimaging in children with uncomplicated migraine and normal neurological examination was 3.7%. The yield in children with chronic daily headache and normal neurological examination was higher at 16.6%. The abnormalities discovered included arachnoid cysts, Chiari I malformations, sinus disease, occult vascular malformations and "dilated Virchow-Robin spaces." While none of the neuroimaging findings were apparent clinically, their discovery did not influence the diagnosis, management, or outcome of the patients. None of the abnormalities necessitated surgical intervention or were associated with the headache presentation. Therefore, neuroimaging is not warranted in children and adolescents with defined clinical headache syndrome diagnoses whose neurological examinations are normal.

Acute headache in children and adolescents presenting to the emergency department.

OBJECTIVES: Our goals were (1) to investigate the causes of acute headache in childhood from the emergency department perspective and (2) to search for clinical clues that might distinguish headache associated with serious underlying disease. BACKGROUND: The clinical presentation of headache in children and adolescents can be separated into 5 temporal patterns: acute, acute-recurrent, chronic progressive, chronic nonprogressive, and mixed. Few data exist regarding acute headache in children. METHODS: Consecutive children who presented to our emergency department with the abrupt onset of severe headache were prospectively evaluated. The headache character, location, severity, and associated symptoms, as well as underlying causes, were recorded using a standardized survey. RESULTS: One hundred fifty children, aged from 2 to 18 years, 87 boys and 63 girls, were enrolled over a 10-month period. Upper respiratory tract infection with fever (viral upper respiratory tract infection 39%, sinusitis 9%, streptococcal pharyngitis 9%) was the most frequently identified cause of acute headache (57%). Other causes included migraine (18%), viral meningitis (9%), posterior fossa tumors (2.6%), ventriculoperitoneal shunt malfunction (2%), epileptic seizure (postictal headache) (1.3%), concussion (postconcussive headache) (1. 3%), intracranial hemorrhage (1.3%), and undetermined (7%). Two clinical features were found to have statistically significant associations with serious underlying disease: occipital location of headache and an inability of the patient to describe the quality of the head pain. All children with surgically remediable conditions had clear and objective neurological signs. CONCLUSIONS: In children and adolescents, the abrupt onset of severe headache is most frequently caused by upper respiratory tract infection with fever, sinusitis, or migraine. Special attention is warranted if the acute headache is occipital in location and if the affected patient is unable to describe the quality of the pain. Serious underlying processes such as brain tumor or intracranial hemorrhage are uncommon and, when present, are accompanied by multiple neurological signs (ataxia, hemiparesis, papilledema).

How competent do our graduates feel?

As part of a review of the undergraduate curriculum to assess its relevance for a future general practitioner, a survey of self-perceived competency at graduation based on the competency list developed by the Association of Canadian Faculties of Dentistry was circulated to recent graduates and the graduating class. The overall response was 67.5 percent, and revealed that approximately 70 percent of the respondents felt well prepared in approximately 69 percent of the competencies. These were the common "bread and butter" items of dentistry, such as basic restorative dentistry, examination, diagnosis, treatment planning, local anaesthesia, and scaling. Those areas reported as less well-prepared for included financial and personnel management, performance of soft-tissue biopsies, and management of chronic orofacial pain. Clarification of the raw survey results in focus groups was needed to uncover specific details that could lead to remedial action in problem areas.

Optimized therapy for the edentulous predicament: cost-effectiveness considerations.

After proof of the clinical effectiveness of prosthodontic interventions, comparative economic analyses (cost-effectiveness, cost benefit, cost utility) should be undertaken to establish the relative value of each intervention in terms of its costs and consequences. Over time, these analyses must consider the balance between each intervention's initial and maintenance costs versus a broad array of clinician and patient-based multidimensional benefits or outcomes. The findings of current research will enhance increased economic analysis in prosthodontics, which, in turn, may help both dentists' and patients' decision-making. Even implant-supported prostheses that are clinically effective have yet to be proven societally effective because they are inaccessible economically to some who need them. Long-term, multidimensional comparative economic analyses of overdenture and conventional denture use may lead to the expansion of implant-supported dentures to selected patients who, to date, have not had access to this treatment modality.

Dental caries knowledge in a group of Northwest Territories children.

A total of 953 children in schools in communities in the Northwest Territories was surveyed to determine their attitudes and knowledge about dental decay. A questionnaire was answered by these Native and non-Native children in the Northwest Territories. The median age of the children was 12.5 years. The girls tended to brush their teeth more frequently and consumed less sugared sweets between meals. More of the girls and in particular the Native girls knew about "nursing" caries. The Native students more often than not went for dental treatment when it was necessary. The Native students brushed their teeth less frequently and often learned to brush their teeth on their own. The consumption of sugared sweets between meals was greater in the Native sample. The knowledge level of the factors that affect dental decay rates was lower in the Native group, but was not extremely high in either group. These children should receive more information on oral health practices and be given an opportunity to improve their oral health knowledge.

Influence of the addition of restorations on the diagnosis of caries from digitized bitewing radiographs.

OBJECTIVES: The purpose of this study was to assess the influence of additional caries and restorations on the detection of caries on the same radiograph. STUDY DESIGN: Six participants examined five series of four radiographs in which natural carious lesions were present. Each series consisted of the same image with progressively more restorative treatment digitally painted on. The films were randomly presented to the observers who examined the films for the presence and depth of carious lesions. The observers were not informed that the 20 films were disguised versions of the same original five radiographs. RESULTS: The number of carious lesions reported by the six observers did not increase despite the apparent increased restorative intervention viewed on the radiographs. CONCLUSIONS: The complexity of restorative care does not affect observers' ability to correctly detect approximal carious lesions.

A survey of general dentists in Ontario, Part II: Knowledge and use of topical fluoride and dental prophylaxis practices.

A mail questionnaire was used to assess variations in the knowledge and practices of Ontario dentists with respect to topical fluoride and prophylaxis procedures. The questionnaire was answered by 1,276 general dentists. A high percentage (72 to 83 per cent) of respondents identified six months as the optimal time interval at which both procedures should be repeated for all patients under 19 years of age. Relatively few dentists (< 10 per cent) indicated that there should be no specific time interval for re-treatment (i.e. that it should be individually selected). The respondents' preventive knowledge was found to be deficient in two areas: few dentists (16 per cent) knew that it is not necessary to provide a prophylaxis prior to topical fluoride application to achieve maximum caries protection; and most dentists overestimated the speed of caries progress from outer enamel to the dentinoenamel junction (DEJ) in both primary (83 per cent) and permanent (82 per cent) approximal tooth surfaces. In bivariate analysis, three variables were found to be consistently and significantly related to optimal time intervals selected for both topical fluoride application and prophylaxis procedures: year of graduation from dental school; level of hygienist employment; and percentage of patients with private insurance. Multivariate analysis also identified three significant variables: year of graduation from dental school; level of dental hygienist employment; and practice business. Continuing education courses are suggested as a means of updating dentists' knowledge regarding preventive services. Studies are needed to determine the extent to which recent recommendations regarding the professional application of topical fluorides have been followed.

A survey of general dentists in Ontario, Part I: Sealant use and knowledge.

This study assessed the use of pit and fissure sealants by Ontario dentists, as well as variations in the knowledge and practices of this population with respect to certain aspects of the preventive technique. A mail questionnaire on dental practices and knowledge was answered by 1,276 general dentists in Ontario. Most dentists (90 per cent) provided sealants to their patients, and reported using sealants on an average of 45 per cent of their patients between the ages of six and 16 years. While most dentists knew that sealants have been proven effective in preventing caries (90 per cent), many incorrectly believed that sealants are cost-effective to apply to both primary molars and permanent premolars (40 per cent and 68 per cent respectively). Bivariate analyses showed that many of the reported characteristics are statistically significant. The variables that were consistently associated with sealant use include: knowledge of the effectiveness and cost-effectiveness of sealants; year of graduation from dental school; level of dental hygienist employment; and continuing education participation. Although multivariate analyses identified many of these variables as statistically significant, only a moderate amount of the variation in sealant use for patients aged six to 16 was explained (R2 = 0.22). Due to misinformation about the cost-effectiveness of sealants, some dentists may overuse them in certain instances. Conversely, misinformation about the effectiveness of sealants and the risk of further decay after sealant placement has resulted in some dentists under-utilizing them. Continuing education courses are needed to update dentists' knowledge and beliefs regarding dental sealants. In addition, dentistry's professional bodies should develop clinical practice guidelines to aid dentists in their treatment planning decisions.

L-[1-(13)C] Phenylalanine oxidation as a measure of hepatocyte functional capacity in end-stage liver disease.

BACKGROUND: Liver disease is associated with impaired metabolism of these amino acids phenylalanine and tyrosine. Decreased metabolism of these amino acids leads to abnormal plasma elevations and impaired clearance rates. We have developed a noninvasive breath test that measures hepatic cytosolic enzyme activity. METHODS: The rate of hepatic phenylalanine metabolism was quantitatively calculated from the appearance of 13CO2 in the breath using the nonradioactive tracer L-[1-(13)C]phenylalanine. RESULTS: Normal controls (n = 47) oxidized phenylalanine more than twice that of end-stage liver disease patients (n = 117). Significant differences in the percent of phenylalanine oxidized per hour (mean +/- SEM) were found between controls (7.08% +/- 0.33%, 95% CI: 6.42%-7.74%) and Child Pugh classification patients, class A (4.96% +/- 0.69%, 95% CI: 3.50%-6.42%), class B (2.88% +/- 0.13, 95% CI: 2.39%-3.38%) and class C (1.75% +/- 0.13, 95% CI: 1.50%-2.01%). The phenylalanine breath test score significantly correlated with albumin levels, prothrombin time and total bilirubin. CONCLUSION: We have demonstrated that phenylalanine oxidation is significantly decreased with end-stage liver disease and is correlated with the best clinical measures of liver disease.

Restorative certainty and varying perceptions of dental caries depth among dentists.

OBJECTIVE: The question of whether dentists who most frequently identify tooth surfaces for definite restoration perceive dental caries as significantly deeper than other dentists is assessed. METHODS: One group of 20 dentists independently examined 145 unrestored approximal tooth surfaces on 16 bitewing radiographs and recorded their restorative and depth decisions. Another group of 15 dentists similarly scored 304 unrestored surfaces on 30 bitewing radiographs. Each group of dentists was later divided into four subgroups according to the number of surfaces designated for definite restoration by each dentist. RESULTS: As the number of tooth surfaces designated for definite restoration increased, mean caries depth (P < .05 for the high vs low subgroups) and the percent of dentinally carious surfaces increased, while the percent of surfaces assessed as sound decreased. Dentists with the lower numbers of surfaces designated for definite restoration came closest to the true histologic mean caries depth of the examined tooth surfaces. CONCLUSIONS: Dentists who designated high numbers of approximal tooth surfaces for definite restoration assessed caries as deeper than other dentists, and deeper than was proven histologically.