Morphological study of dentin irradiated by solid-state ultraviolet lasers: a comparison of wavelength and repetition rate

OBJECTIVE: In this study, we examined the surface morphology of dentin after being ablated by the third, fourth, and fifth harmonics of the Nd:YAG laser. The influences of the repetition rate with respect to the wavelength were also investigated. BACKGROUND DATA: Typically, excimer lasers have been used as the primary sources of ultraviolet (UV) laser wavelengths to investigate laser ablation of dentin. In the past decade, developments in nonlinear optical technology have given rise to higher conversion efficiencies of the fourth and fifth harmonics of the Nd:YAG laser. To this end, sufficient energy densities of the fourth and fifth harmonics of the Nd:YAG laser have been generated to ablate dentin. MATERIALS AND METHODS: Thin dentin samples (typically 1 mm) were irradiated by the third, fourth, and fifth harmonics of the Nd:YAG laser. Ablation occurred at repetition rates of 1, 5, 10, and 20 Hz, using similar energy densities for each laser wavelength. An environmental scanning electron microscope was used to assess the resultant surface morphology. RESULTS: Dentine surfaces after 355-nm ablation exhibited plugging at each repetition rate. Similar surfaces were exhibited after 266-nm ablation. "Plugging" over dentine tubules was less obvious after 213-nm laser ablation. The results may highlight the impact of different absorption characteristics of each wavelength. CONCLUSION: Solid-state UV laser ablation of dentin exhibits similar properties to excimer laser ablation. At similar energy densities, the deeper UV laser wavelengths exhibit less "plugging" of dentin tubules, suggesting a lower thermal impact.     

Comorbidity and correlates of disruptive mood dysregulation disorder in 6–8-year-old children with ADHD

This study aimed to characterize the nature and impact of disruptive mood dysregulation disorder (DMDD) in children with attention-deficit/hyperactivity disorder (ADHD) including its co-occurrence with other comorbidities and its independent influence on daily functioning. Children with ADHD (6–8 years) were recruited through 43 Melbourne schools, using a 2-stage screening (parent and teacher Conners 3 ADHD index) and case-confirmation (Diagnostic Interview Schedule for Children, Version IV; [DISC-IV]) procedure. Proxy DMDD diagnosis was confirmed via items from the oppositional defiant disorder (ODD) and major depressive disorder modules of the DISC-IV. Outcome domains included comorbid mental health disorders, academic functioning, social functioning, child and family quality of life, parent mental health, and parenting behaviors. Unadjusted and adjusted linear and logistic regression were used to compare children with comorbid ADHD and DMDD and children with ADHD without DMDD. Thirty-nine out of 179 children (21.8 %) with ADHD had comorbid DMDD. Children with ADHD and DMDD had a high prevalence of ODD (89.7 %) and any anxiety disorder (41.0 %). Children with ADHD and DMDD had poorer self-control and elevated bullying behaviors than children with ADHD without DMDD. Children with ADHD and DMDD were similar to children with ADHD in the other domains measured when taking into account other comorbidities including ODD. One in five children with ADHD in their second year of formal schooling met criteria for DMDD. There was a very high diagnostic overlap with ODD; however, the use of a proxy DMDD diagnosis containing items from the ODD module of the DISC-IV may have artificially inflated the comorbidity rates. DMDD added to the burden of ADHD particularly in the area of social functioning.     

Pharmacokinetics of total and unbound ertapenem in healthy elderly subjects

Ertapenem is a new once-a-day parenteral carbapenem antimicrobial agent. The pharmacokinetics of unbound and total concentrations of ertapenem in plasma were investigated in elderly subjects and compared with historical data from young adults. In a single- and multiple-dose study, healthy elderly males and females (n = 14) 65 years old or older were given a 1-g intravenous (i.v.) dose once daily for 7 days. Plasma and urine samples collected for 24 h on days 1 and 7 following administration of the 1-g doses were analyzed by reversed-phase high-performance liquid chromatography. Areas under the concentration-time curve from 0 h to infinity (AUC(0- infinity )) for elderly females and males were similar following administration of 1-g single i.v. doses, and thus, the genders were pooled in subsequent analyses. Concentrations in plasma and the half-life of ertapenem were generally higher and longer, respectively, in elderly subjects than in young adults. The mean AUC(0- infinity ) of total ertapenem in the elderly was 39% higher than that in young subjects following administration of a 1-g dose. The differences were slightly greater for the mean AUC(0- infinity ) of unbound ertapenem (71%). The unbound fraction of ertapenem in elderly subjects ( approximately 5 to 11%) was generally greater than that in young adults ( approximately 5 to 8%). As in young adults, ertapenem did not accumulate upon multiple dosing in the elderly. The pharmacokinetics of ertapenem in elderly subjects, while slightly different from those in young adults, do not require a dosage adjustment for elderly patients.     

Review of prospective longitudinal studies of children with ADHD: Mental health, educational, and social outcomes

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood, resulting in impairments in academic, mental health, and functional domains. Whereas the short-term effects of ADHD are well documented, much less is understood about the adolescent and adult outcomes of children diagnosed with ADHD. This article attempts to increase understanding of these outcomes by providing an integrated summary of prospective longitudinal cohort studies investigating the outcomes of children with ADHD. Particular focus is paid to mental health, educational, and social outcomes, in addition to ADHD persistence. Overall, the data show that children with ADHD experience serious functional deficits across domains in adolescence and early-adulthood. Furthermore, the impairing symptoms of ADHD do not disappear in adulthood, as was once thought. We hope that through improved understanding of risk and protective factors in ADHD, clinicians, families, and schools can better help children with ADHD reach their full potential.     

Occupancy of human brain GABAA receptors by the novel α5 subtype-selective benzodiazepine site inverse agonist α5IA as measured using [11C]flumazenil PET imaging

GABA_A receptor α5-selective inverse agonists enhance cognitive performance in pre-clinical species. However, a key aspect of the clinical development of such compounds is the demonstration that in man such compounds are devoid of the anxiogenic-like activity associated with non-selective inverse agonists such as FG 7142. The triazolophthalazine α5IA (3-(5-methylisoxazol-3-yl)-6-[(1-methyl-1,2,3-triazol-4-yl)methyloxy]-1,2,4-triazolo[3,4-a]phthalazine) is an α5-selective inverse agonist which enhances cognitive performance in rodents and encouragingly in human Phase I Safety and Tolerability studies it was devoid of the anxiogenic-like activity associated with FG 7142. However, in order to appropriately interpret this latter observation, it was considered important to demonstrate that the absence of anxiogenic-like activity occurs at significant levels of receptor occupancy. Consequently, the occupancy of human brain GABA_A receptors was measured using [¹¹C]flumazenil positron emission tomography in three healthy normal young male volunteers following a single oral dose of 2 mg α5IA. One hour after dosing, mean occupancy levels were 53% and this fell to 16% by 8 h post-dose, with the plasma α5IA concentration corresponding to 50% occupancy being 10 ng/mL. These data clearly show that an α5-selective inverse agonist is not associated with anxiogenic-like side effects at doses that give ～50% occupancy.